RMS can occur in almost any soft-tissue site in the body; the most common primary sites are genitourinary (24%), parameningeal (16%), extremity (19%), orbit (9%), other head and neck (10%), and miscellaneous other sites (22%). RMS often presents as a mass, but signs and symptoms can vary widely depending on the site of the primary tumor. Genitourinary tumors may present with hematuria, urinary tract obstruction, and/or a scrotal or vaginal mass. Tumors that arise in the retroperitoneum and mediastinum can become quite large before producing signs and symptoms. Parameningeal tumors may present with cranial nerve dysfunction, symptoms of sinusitis, ear discharge, headaches, and facial pain. Orbital tumors often present with orbital swelling and proptosis. Extremity tumors generally present as a rapidly enlarging, firm mass in the relevant tissue. The cancer's prevalence in the head, face, and neck will often allow for earlier signs of the disease simply due to the obvious nature of tumors in these locations. Despite the varying presentation and typically aggressive nature of the disease, RMS has the potential to be diagnosed and treated early. The fourth IRSG study found that 23% of patients were diagnosed in time for a complete resection of their cancer, and 15% had resection with only minimal remnants of the diseased cells.

Mast cell tumors are known among veterinary oncologists as 'the great pretenders' because their appearance can be varied, from a wart-like nodule to a soft subcutaneous lump (similar on palpation to a benign lipoma) to an ulcerated skin mass. Most mast cell tumors are small, raised lumps on the skin. They may be hairless, ulcerated, or itchy. They are usually solitary, but in about six percent of cases, there are multiple mast cell tumors (especially in Boxers and Pugs).

Manipulation of the tumor may result in redness and swelling from release of mast cell granules, also known as Darier's sign, and prolonged local hemorrhage. In rare cases, a highly malignant tumor is present, and signs may include loss of appetite, vomiting, diarrhea, and anemia. The presence of these signs usually indicates mastocytosis, which is the spread of mast cells throughout the body. Release of a large amount of histamine at one time can result in ulceration of the stomach and duodenum (present in up to 25 percent of cases) or disseminated intravascular coagulation. When metastasis does occur, it is usually to the liver, spleen, lymph nodes and bone marrow.

In general, epithelioid sarcoma is a slow-growing and relatively painless tumor, often resulting in a lengthy period of time between presentation and diagnosis. Due to its ambiguity, it is often misdiagnosed, mistaken as a persistent wart or cyst. It most commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) as a small, soft mass or a series of bumps. It is most often described as a firm-to-hard palpable mass, either in the deep soft tissue or in the dermis. Often, superficial lesions will ulcerate causing a mistaken diagnosis of a poorly healing traumatic wound or wart. About 13% of patients will present with multifocal tumors, and about 13% of patients will present with metastatic disease.

It presents as a slow growing mass that especially affects tendons and aponeuroses and it is deeply situated. Patients often perceive it as a lump or hard mass. It causes either pain or tenderness but only until it becomes large enough. This kind of tumor is commonly found in the extremities especially around the knee, feet and ankle. Patients diagnosed with clear cell sarcoma are usually between the ages of 20 and 40.

When mastocytomas affect humans, they are typically found in skin. They usually occur as a single lesion on the trunk or wrist. Although it is rare, mastocytomas are sometimes found in the lung. It can also affect children.

Epithelioid sarcoma is a rare soft tissue sarcoma arising from Mesenchyme tissue and characterized by epithelioid-like features. It accounts for less than 1% of all soft tissue sarcomas. It was first clearly characterized by F.M. Enzinger in 1970. It commonly presents itself in the distal limbs (fingers, hands, forearms, or feet) of young adults as a small, soft mass or a series of bumps. A proximal version has also been described, frequently occurring in the upper extremities. Rare cases have been reported in the pelvis, vulva, penis, and spine.

Histologically, epithelioid sarcoma forms nodules with central necrosis surrounded by bland, polygonal cells with eosinophilic cytoplasm and peripheral spindling. Epithelioid sarcomas typically express vimentin, cytokeratins, epithelial membrane antigen, and CD34, whereas they are usually negative for S100, desmin, and FLI-1. They typically stain positive for CA125.

Epithelioid sarcoma most commonly strikes young adults, yet no age group is immune. The disease has a tendency to develop local recurrences and metastasis thereafter to regional lymph nodes, lung, bone, brain, and other locations, including the scalp. Generally speaking, epithelioid sarcoma has a high rate of relapse after initial treatment and tends to recur locally (at or near the original tumor site). Epithelioid sarcoma also demonstrates lymphatic spread (in 22-48% of cases), and metastasis (in 21-63% of cases). These events, as well as advanced stage (progression) and grade (aggressiveness), are predictive of an overall worse outcome. The overall five-year survival rate for epithelioid sarcoma is anywhere from 25 to 78%. Importantly, the 10-year and 15-year survival rate drops off significantly. Associated with a more positive outcome are younger age, female vs. male sex, distal vs. proximal location, smaller tumor size, and negative margins upon tumor resection.

Ewing's sarcoma is more common in males (1.6 male:1 female) and usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age. It can occur anywhere in the body, but most commonly in the pelvis and proximal long tubular bones, especially around the growth plates. The diaphyses of the femur are the most common sites, followed by the tibia and the humerus. Thirty percent are overtly metastatic at presentation. Patients usually experience extreme bone pain.

Signs and symptoms include: intermittent fevers, anemia, leukocytosis, increased sedimentation rate, and other symptoms of inflammatory systemic illness. Also, depending on the type, progression, and location of the tumor, great pain may occur.

According to the Bone Cancer Research Trust (BCRT), the most common symptoms are: localized pain, swelling, and sporadic bone pain with variable intensity. The swelling is most likely to be visible if the sarcoma is located on a bone near the surface of the body, but when it occurs in other places deeper in the body, like on the pelvis, it may not be visible.

There are few early warning signs that a patient has a DSRCT. Patients are often young and healthy as the tumors grow and spread uninhibited within the abdominal cavity. These are rare tumors and symptoms are often misdiagnosed by physicians. The abdominal masses can grow to enormous size before being noticed by the patient. The tumors can be felt as hard, round masses by palpating the abdomen.

First symptoms of the disease often include abdominal distention, abdominal mass, abdominal or back pain, gastrointestinal obstruction, lack of appetite, ascites, anemia, and/or cachexia.

Other reported symptoms include unknown lumps, thyroid conditions, hormonal conditions, blood clotting, kidney or urological problems, testicle, breast, uterine, vaginal, or ovarian masses.

Given the difficulty in diagnosing rhabdomyosarcoma, definitive classification of subsets has proven difficult. As a result, classification systems vary by institute and organization. However, rhabdomyosarcoma can be generally divided into three histological subsets:

- "Embryonal rhabdomyosarcoma" (ERMS) is the most common histological variant, comprising approximately 60–70% of childhood cases. It is most common in children 0–4 years old, with a maximum reported incidence of 4 cases per 1 million children. ERMS is characterized by spindle-shaped cells with a stromal-rich appearance, and the morphology is similar to the developing muscle cells of a 6–8 week old embryo. Tumors often present in the head and neck as well as the genitourinary tract. ERMS also has two defined subtypes, botryoid and spindle cell ERMS, and these subtypes are associated with a favorable prognosis.

- Subtypes of ERMS

- Botryoid ERMS is almost always found in mucosal lined organs including the vagina, bladder, and nasopharynx (although presentation in the nasopharynx typically affects older children). It often presents in patients <1 year old as a round, grape-like mass on the affected organ. Histologically, cells of the botryoid variant are defined by a dense tumor layer under an epithelium (cambium layer).

- Spindle cell rhabdomyosarcoma comprises about 3% of all RMS cases. This subtype is very similar to that of leiomyosarcoma (cancer of the smooth muscle tissue), and it has a fascicular, spindled, and leiomyomatous growth pattern with notable rhabdomyoblastic differentiation . It occurs most commonly in the paratesticular region, and the prognosis for this particular form of RMS is excellent with a reported 5 year survival rate of 95%.

- "Alveolar rhabdomyosarcoma" (ARMS) is the second most common type. ARMS comprises approximately 20–25% of RMS-related tumors, and it is equally distributed among all age groups with an incidence of about 1 case per 1 million people ages 0 to 19. For this reason, it is the most common form of RMS observed in young adults and teenagers, who are less prone to the embryonal variant. This type of RMS is characterized by densely-packed, round cells that arrange around spaces similar in shape to pulmonary alveoli, although variants have been discovered without these characteristic alveolar spacings. ARMS tends to form more often in the extremities, trunk, and peritoneum. It is also typically more aggressive than ERMS.

- "Anaplastic (undifferentiated) rhabdomyosarcoma", also known as "pleomorphic rhabdomyosarcoma", is the final variant of RMS recognized in most classification systems. Anaplastic rhabdomyosarcoma is defined by the presence of anaplastic cells with large, lobate hyperchromatic nuclei and multipolar mitotic figures. These tumors display high heterogeneity and extremely poor differentiation. The anaplastic cells may be diffuse or localized, with the diffuse variation correlating to a worse prognosis. It occurs most often in adults, rarely in children, and is often discovered in the extremities. Due to the lack of discernible separation among cancers of this type, clinicians will often label undiagnosed sarcomas with little to no discernible features as anaplastic RMS. It is the most aggressive type of RMS, and will often require intensive treatment.

There is also an extremely rare subtype of RMS that has been described as "sclerosing rhabdomyosarcoma" by "Folpe, et al", but it is not a currently recognized subtype by the NCI or WHO. This subtype has characteristic histology involving hyaline sclerosis and pseudovascular development. Its origins are unclear, but some studies have pointed to an association with embryonal RMS.

Multiple classification systems have been proposed for guiding management and treatment, and the most recent and widely used classification system is the "International Classification of Rhabdomyosarcoma" or ICR. It was created by the IRSG in 1995 after their series of four multi-institutional trials aimed at studying the presentation, histology, epidemiology, and treatment of RMS (IRSG I–IV). The ICR system is based on prognostic indicators identified in IRSG I–IV. Pleomorphic rhabdomyosarcoma usually occurs in adults rather than children, and is therefor not included in this system. Sclerosing rhabdomyosarcoma is also not included in this system due to its rare presentation and weak classification schema.

The prognosis for rhabdomyosarcoma has improved greatly in recent decades, with over 70% of patients surviving for five years after diagnosis.

Ewing sarcoma or Ewing's sarcoma () is a malignant small, round, blue cell tumor. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the ribs and clavicle (collar bone).

Since a common genetic locus is responsible for a large percentage of Ewing sarcoma and primitive neuroectodermal tumors, these are sometimes grouped together in a category known as the Ewing family of tumors.

Ewing sarcoma occurs most frequently in teenagers and young adults, with a male/female ratio of 1.6:1.

Although usually classified as a bone tumor, Ewing's sarcoma can have characteristics of both mesodermal and ectodermal origin, making it difficult to classify.

James Ewing (1866–1943) first described the tumour, establishing that the disease was separate from lymphoma and other types of cancer known at that time.

ERMS is the more common of two major subtypes of rhabdomyosarcoma, the other being alveolar rhabdomyosarcoma.

It has been informally classified as a "small round blue cell tumor" because of the characteristic microscopic appearance of its cells after histological staining with hematoxylin and eosin.

When the tumor is large and there is presence of necrosis and local recurrence, the prognosis is poor. Presence of metastasis occurs in more than 50% cases and the common places of its occurrence are the bone, lymph node and lungs. Five-year survival rates, which are reported to be between 50-65%, can be misleading because the disease is prone to late metastasis or recurrence. Ten and twenty-year survival rates are 33% and 10%, respectively.

Giant-cell carcinoma of the lung (GCCL) is a rare histological form of large-cell lung carcinoma, a subtype of undifferentiated lung cancer, traditionally classified within the non-small-cell lung carcinomas (NSCLC).

The characteristic feature of this highly lethal malignancy is the distinctive light microscopic appearance of its extremely large cells, which are bizarre and highly pleomorphic, and which often contain more than one huge, misshapen, pleomorphic nucleus ("syncytia"), which result from cell fusion.

Although it is common in the lung cancer literature to refer to histologically mixed tumors containing significant numbers of malignant giant cells as "giant-cell carcinomas", technically a diagnosis of "giant-cell carcinoma" should be limited strictly to neoplasms containing "only" malignant giant cells (i.e. "pure" giant-cell carcinoma).

Aside from the great heterogeneity seen in lung cancers (especially those occurring among tobacco smokers), the considerable variability in diagnostic and sampling techniques used in medical practice, the high relative proportion of individuals with suspected GCCL who do not undergo complete surgical resection, and the near-universal lack of complete sectioning and pathological examination of resected tumor specimens prevent high levels of quantitative accuracy.

Desmoplastic small-round-cell tumor is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones.

The tumor is classified as a soft tissue sarcoma. It is considered a childhood cancer that predominantly strikes boys and young adults. The disease rarely occurs in females, but when it does the tumors can be mistaken for ovarian cancer.

In dogs, mast cell tumors are the most frequent round cell tumor.

Congenital mesoblastic nephroma typically (76% of cases) presents as an abdominal mass which is detected prenatally (16% of cases) by ultrasound or by clinical inspection (84% of cases) either at birth or by 3.8 years of age (median age ~1 month). The neoplasm shows a slight male preference. Concurrent findings include hypertension (19% of cases), polyhydramnios (i.e. excess of amniotic fluid in the amniotic sac) (15%), hematuria (11%), hypercalcemia (4%), and elevated serum levels of the kidney-secreted, hypertension-inducing enzyme, renin (1%). Congenital anomalies have been reported in 11 patients: 6 with genitourinary anomalies, 2 with gastrointestinal anomalies, 1 with hydrocephalus, and 1 with the Beckwith–Wiedemann syndrome. The vast majority of patients present with localized (i.e. non-metastatic) disease. Most patients' disease is classified at presentation as stage I or II (i.e. localized), few patients present with stage III (i.e. locally advanced/infiltrating), and virtually no patients present with stage IV (metastases present or V (i.e. tumors in both kidneys) disease (see staging of renal cancer).

Patients usually note a deep seated mass in their soft tissue. Only when the tumor is very large do symptoms of pain or functional disturbances occur.

Retroperitoneal tumors may present themselves with signs of weight loss and emaciation and abdominal pain. These tumors may also compress the kidney or ureter leading to kidney failure.

Diagnosis of mesoblastic nephroma and its particular type (i.e. classic, mixed, or cellular) is made by histological examination of tissues obtained at surgery. Besides its histological appearance, various features of this disease aid in making a differential diagnosis that distinguish it from the following childhood neoplasms:

- Wilm's tumor is the most common childhood kidney neoplasm, representing some 85% of cases. Unlike mesoblastic nephroma, 3 years of age. Bilateral kidney tumors, concurrent birth defects, and/or metastatic disease at presentation favor a diagnosis of Wilm's tumor.

- congenital infantile sarcoma is a rare aggressive sarcoma typically presenting in the lower extremities, head, or neck of infants during their first year of life. The histology, association with the "ETV6-NRTK3" fusion gene along with certain chromosome trisomies, and the distribution of markers for cell type (i.e. cyclin D1 and Beta-catenin) within this tumor are the same as those found in cellular mesoblastic nephroma. Mesoblastic nephroma and congenital infantile sarcoma appear to be the same diseases with mesoblastic lymphoma originating in the kidney and congenital infantile sarcoma originating in non-renal tissues.

- Rhabdoid tumor, which accounts for 5-510% of childhood kidney neoplasms, occurs predominantly in children from 1 to 2 years of age. Unlike mesoblastic nephroma, rhabdoid tumors may present with tumors in other tissues including in ~13% of cases, the brain. Rhabdoid tumors have a distinctive histology and abnormalities (i.e. loss of heterozygosity, single nucleotide polymorphism, and deletions) in chromosome 22.

- Clear cell sarcoma of the kidney, which is responsible for 5-10% of childhood pediatric tumors, occurs predominantly in children from 2 to 3 years of age. Unlike meoblastic nephorma, clear cell sarcoma of the kidney presents with metastasis, particularly to bone, in 5-6% of cases; it histology is diverse and has been mistaken for mesoblastic nephroma. One chromosomal translocations t,(10;17)(q22;p13), has been repeatedly reported to be associated with clear cell sarcoma of the kidney.

- Infantile myofibromatosis is a fibrous tumor of infancy and childhood most commonly presenting during the first 2 years of life as a single subcutaneous nodule of the head and neck region or less commonly as multiple lesions of skin, muscle, bone, and in ~33% of these latter cases, visceral organs. All of these lesions have an excellent prognosis and can regress spontaneously except for those in which there is visceral involvement where the prognosis is poor. While infantile myofibromatosis and classic mesoblastic nephroma have been suggested to be the same diseases because of their very similar histology, studies on the distribution of cell-type markers (i.e. cyclin D1 and Beta-catenin) indicate that they have different cellular origins.

For several decades, primary lung cancers were consistently dichotomously classified for treatment and research purposes into small-cell lung carcinomas (SCLCs) and non-small-cell lung carcinomas (NSCLCs), based on an oversimplified approach that is now clearly outmoded. The new paradigm recognizes that lung cancers are a large and extremely heterogeneous family of malignant neoplasms, with over 50 different histological variants included in the 4th (2004) revision of the World Health Organization typing system, the most widely used lung cancer classification scheme ("WHO-2004"). These variants are increasingly appreciated as having different genetic, biological, and clinical properties, including prognoses and responses to treatment regimens, and therefore, that correct and consistent histological classification of lung cancers are necessary to validate and implement optimum management strategies.

About 1% of lung cancers are sarcomas, germ cell tumors, and hematopoietic tumors, while 99% of lung cancers are carcinoma. Carcinomas are tumors composed of transformed, abnormal cells with epithelial tissue architecture and/or molecular characteristics, and which derive from embryonic endoderm. Eight major taxa of lung carcinomas are recognized within the WHO-2004 classification:

1. Small-cell carcinoma

2. Squamous cell carcinoma

3. Adenocarcinoma

4. Large-cell carcinoma

5. Adenosquamous carcinoma

6. Sarcomatoid carcinoma

7. Carcinoid

8. Salivary gland-like carcinoma

The subclassification of GCCL among these major taxa has undergone significant changes in recent decades. Under the 2nd revision (1981) of the WHO classification, it was considered a subtype of large-cell carcinoma. In the 3rd (1999) revision, it was placed within a taxon called "Carcinomas with Pleomorphic, Sarcomatoid, or Sarcomatous Elements", along with pleomorphic carcinoma, spindle cell carcinoma, carcinosarcoma, and pulmonary blastoma, which are (arguably) related variants. While the 4th revision ("WHO-2004") retained the same grouping of lesions as the 3rd revision, the name of the major taxon was shortened to "sarcomatoid carcinomas".

The current rules for classifying lung cancers under WHO-2004, while useful and improved, remain to some extent fairly complex, ambiguous, arbitrary, and incomplete. Although it is fairly common for mixed tumors that are seen to contain malignant giant cells to be called "giant-cell carcinomas", "accurate" classification of a pulmonary tumor as a GCCL requires that the "entire tumor" consists "only" of malignant giant cells. Therefore, complete sampling of the entire tumor — obtained via a surgical resection — is absolutely necessary for a definitive diagnosis of GCCL to be made.

Esthesioneuroblastoma will first frequently present as a nasal mass. The most common signs and symptoms of esthesioneuroblastoma are nasal obstruction (70%) and epistaxis (50%). Less common symptoms include hyposmia (loss of smell), headache, rhinorrhea, vision loss, proptosis, facial pain, diplopia (double vision), masses in the neck and changes in mental status. Esthesioneuroblastoma occurs in the upper nasal cavity, near the optic nerves and optic chiasm. Thus, tumor growth can impinge nerve function and result in vision loss and diplopia. As the tumor metastasizes to the oral cavity, there can be tooth pain and tooth mobility.

MCC usually presents as a firm, painless, nodule (up to 2 cm diameter) or mass (>2 cm diameter). These flesh-colored, red, or blue tumors typically vary in size from 0.5 cm (less than one-quarter of an inch) to more than 5 cm (2 inches) in diameter, and usually enlarge rapidly. Although MCC's may arise almost anywhere on the body, about half originate on sun-exposed areas of the head and neck, one-third on the legs, and about one-sixth on the arms. In about 12% of cases, no obvious anatomical site of origin ("primary site") can be identified.

Merkel-cell cancers tend to invade locally, infiltrating the underlying subcutaneous fat, fascia, and muscle, and typically metastasize early in their natural history, most often to the regional lymph nodes. MCCs also spread aggressively through the blood vessels, particularly to liver, lung, brain, and bone.

Liposarcoma is a cancer that arises in fat cells in deep soft tissue, such as that inside the thigh or in the retroperitoneum. Liposarcoma is a rare type of cancer that bears a resemblance to fat cells when examined under a microscope.

They are typically large bulky tumors, and tend to have multiple smaller satellites that extend beyond the main confines of the tumor.

Liposarcomas, like all sarcomas, are rare.

The first symptoms of neuroblastoma are often vague making diagnosis difficult. Fatigue, loss of appetite, fever, and joint pain are common. Symptoms depend on primary tumor locations and metastases if present:

- In the abdomen, a tumor may cause a swollen belly and constipation.

- A tumor in the chest may cause breathing problems.

- A tumor pressing on the spinal cord may cause weakness and thus an inability to stand, crawl, or walk.

- Bone lesions in the legs and hips may cause pain and limping.

- A tumor in the bones around the eyes or orbits may cause distinct bruising and swelling.

- Infiltration of the bone marrow may cause pallor from anemia.

Neuroblastoma often spreads to other parts of the body before any symptoms are apparent and 50 to 60% of all neuroblastoma cases present with metastases.

The most common location for neuroblastoma to originate (i.e., the primary tumor) is in the adrenal glands. This occurs in 40% of localized tumors and in 60% of cases of widespread disease. Neuroblastoma can also develop anywhere along the sympathetic nervous system chain from the neck to the pelvis. Frequencies in different locations include: neck (1%), chest (19%), abdomen (30% non-adrenal), or pelvis (1%). In rare cases, no primary tumor can be discerned.

Rare but characteristic presentations include transverse myelopathy (tumor spinal cord compression, 5% of cases), treatment-resistant diarrhea (tumor vasoactive intestinal peptide secretion, 4% of cases), Horner's syndrome (cervical tumor, 2.4% of cases), opsoclonus myoclonus syndrome and ataxia (suspected paraneoplastic cause, 1.3% of cases), and hypertension (catecholamine secretion or renal artery compression, 1.3% of cases).

GISTs may present with trouble swallowing, gastrointestinal bleeding, or metastases (mainly in the liver). Intestinal obstruction is rare, due to the tumor's outward pattern of growth. Often, there is a history of vague abdominal pain or discomfort, and the tumor has become rather large by time the diagnosis is made.

AT/RT may be related to malignant rhabdoid tumor (MRT), which occurs outside the CNS, usually in the kidney. The finding that AT/RT and MRT both have deletions of the "INI1" gene indicates that rhabdoid tumors of the kidney and brain are at least closely related. AT/RT and MRT also have similar histology and similar clinical and demographic features. Moreover, 10–15% of MRT patients have simultaneous or subsequent brain tumors, many of which are secondary or primary MRT.