Many patients first complain of pain that may be worse at night, may be intermittent and of varying intensity and may have been occurring for some time. Teenagers who are active in sports often complain of pain in the lower femur, or immediately below the knee. If the tumor is large, it can present as overt localised swelling. Sometimes a sudden fracture is the first symptom, because affected bone is not as strong as normal bone and may fracture abnormally with minor trauma. In cases of more deep-seated tumors that are not as close to the skin, such as those originating in the pelvis, localised swelling may not be apparent.

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.

An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignant osteoid.

Osteosarcoma is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults.

Patients usually present with pain and limited range of motion caused by tumor's proximity to the joint space. Swelling may occur, as well, if the tumor has been growing for a long time. Some patients may be asymptomatic until they develop a pathologic fracture at the site of the tumor. They usually originate from the epiphysis of long bones, but in rare cases, they may arise from anterior arc of the ribs.

The symptoms may include muscular aches and pains in arms or legs and abdominal pain. Patients may also experience nerve pain which feels like an electric shock due to weight bearing.

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.

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).

Childhood rhabdomyosarcoma consists of three subgroups. Embryonal is the most common among children and young adults. Alveolar and anaplastic rhabdomyosarcoma occur in the teenage years.

- Embryonal rhabdomyosarcoma develops within the first seven weeks of the embryo's development. Rapid cell growth causes masses to form along the head, neck, urinary tract, and genital organs.

- Alveolar, the second most common group, is seen later in life. During the teen years, large muscle groups come under attack, including the torso and large appendages. Aggressive treatment is needed to stop or limit progression of alveolar rhabdomyosarcoma.

- Anaplastic rhabdomyosarcoma is rarely seen in children and only precise intensive lab work can identify it.

Childhood rhabdomyosarcoma is difficult to diagnose. Factors that increase the likelihood of this cancer include Li-Fraumeni syndrome, type one Neurofibromatosis, Beckwith-Wiedemann syndrome, Costello syndrome, and Noonan syndrome. Each contribute to deformations of bones, tissue, and muscles.

Congenital mesoblastic nephroma, while rare, is the most common kidney neoplasm diagnosed in the first three months of life and accounts for 3-5% of all childhood renal neoplasms. This neoplasm is generally non-aggressive and amenable to surgical removal. However, a readily identifiable subset of these kidney tumors has a more malignant potential and is capable of causing life-threatening metastases. Congenital mesoblastic nephroma was first named as such in 1967 but was recognized decades before this as fetal renal hamartoma or leiomyomatous renal hamartoma.

Giant-cell tumor of the bone (GCTOB) is a relatively uncommon tumor of the bone. It is characterized by the presence of multinucleated giant cells (osteoclast-like cells). Malignancy in giant-cell tumor is uncommon and occurs in about 2% of all cases. However, if malignant degeneration does occur, it is likely to metastasize to the lungs. Giant-cell tumors are normally benign, with unpredictable behavior. It is a heterogeneous tumor composed of three different cell populations. The giant-cell tumour stromal cells (GCTSC) constitute the neoplastic cells, which are from an osteoblastic origin and are classified based on expression of osteoblast cell markers such as alkaline phosphatase and osteocalcin. In contrast, the mononuclear histiocytic cells (MNHC) and multinucleated giant cell (MNGC) fractions are secondarily recruited and comprise the non-neoplastic cell population. They are derived from an osteoclast-monocyte lineage determined primarily by expression of "CD68", a marker for monocytic precursor cells. In most patients, the tumors are slow to develop, but may recur locally in as many as 50% of cases.

Dogs with limb osteosarcoma typically show lameness and swelling at the affected site. For other sites, dogs may show difficulty to open their mouth (if jaw bone cancer), nasal discharge (if nasal cavity bone cancer) or neurological signs (if spine bone cancer).

Patients with osteoblastoma usually present with pain of several months' duration. In contrast to the pain associated with osteoid osteoma, the pain of osteoblastoma usually is less intense, usually not worse at night, and not relieved readily with salicylates (aspirin and related compounds). If the lesion is superficial, the patient may have localized swelling and tenderness. Spinal lesions can cause painful scoliosis, although this is less common with osteoblastoma than with osteoid osteoma. In addition, lesions may mechanically interfere with the spinal cord or nerve roots, producing neurologic deficits. Pain and general weakness are common complaints.

The Ewing family of tumors is a group of cancers that includes Ewing tumor of bone (ETB or Ewing sarcoma of bone), extraosseous Ewing tumors (EOE tumors), primitive neuroectodermal tumors (PNET or peripheral neuroepithelioma), and Askin tumors (PNET of the chest wall). These tumors all come from the same type of stem cell. Also called EFTs.

Osteoblastoma is an uncommon osteoid tissue-forming primary neoplasm of the bone.

It has clinical and histologic manifestations similar to those of osteoid osteoma; therefore, some consider the two tumors to be variants of the same disease, with osteoblastoma representing a giant osteoid osteoma. However, an aggressive type of osteoblastoma has been recognized, making the relationship less clear.

Although similar to osteoid osteoma, it is larger (between 2 and 6 cm).

A bone tumor (also spelled bone tumour) is a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign (noncancerous) or malignant (cancerous).

Average five-year survival in the United States after being diagnosed with bone and joint cancer is 67%.

A sarcoma is a cancer that arises from transformed cells of mesenchymal origin. Thus, malignant tumors made of cancellous bone, cartilage, fat, muscle, vascular, or hematopoietic tissues are, by definition, considered sarcomas. This is in contrast to a malignant tumor originating from epithelial cells, which are termed carcinoma. Human sarcomas are quite rare. Common malignancies, such as breast, colon, and lung cancer, are almost always carcinoma. The term is from the Greek "sarx" meaning "flesh".

Bone tumors may be classified as "primary tumors", which originate in bone or from bone-derived cells and tissues, and "secondary tumors" which originate in other sites and spread (metastasize) to the skeleton. Carcinomas of the prostate, breasts, lungs, thyroid, and kidneys are the carcinomas that most commonly metastasize to bone. Secondary malignant bone tumors are estimated to be 50 to 100 times as common as primary bone cancers.

The most common bone tumor is called osteosarcoma, and typically affects middle-age to older dogs of large and giant breeds. Osteosarcoma is less common in cats. Osteosarcoma is an aggressive cancer that can develop in any bone of the body but the majority is seen in the limbs (e.g. long bones such as radius, humerus, femur, and tibia).

Sarcomas are given a number of different names based on the type of tissue that they most closely resemble. For example, osteosarcoma resembles bone, chondrosarcoma resembles cartilage, liposarcoma resembles fat, and leiomyosarcoma resembles smooth muscle.

In a case series of 34 patients, Davis and colleagues reported the following signs and symptoms:

- macroscopically visible (gross) hematuria (60%)

- abdominal or back/flank pain (50%)

- significant weight loss (25%)

Other researchers have reported a palpable renal mass or enlarged lymph nodes.

The afflicted may have relatively small amounts of pain that will quickly increase in severity over a time period of 6–12 weeks. The skin temperature around the bone may increase, a bony swelling may be evident, and movement may be restricted in adjacent joints.

Spinal lesions may cause quadriplegia and patients with skull lesions may have headaches.

Aneurysmal bone cyst, abbreviated ABC, is an osteolytic bone neoplasm characterized by several sponge-like blood or serum filled, generally non-endothelialized spaces of various diameters.

The term is a misnomer, as the lesion is neither an aneurysm nor a cyst.

Renal medullary carcinoma has been termed "the seventh sickle cell nephropathy" because it is found almost exclusively in individuals with sickle cell trait or occasionally in those with sickle cell disease.

Most initial symptoms of leukemia are similar to symptoms for irregular bone-marrow function. Typically, most symptoms do not occur during the early stages of leukemia, and children may experience different symptoms. The following are symptoms of leukemia that lead doctors to look for different types of juvenile leukemia:

The classical LFS malignancies - sarcoma, cancers of the breast, brain and adrenal glands - comprise about 80% of all cancers that occur in this syndrome.

The risk of developing any invasive cancer (excluding skin cancer) is ~50% by age 30 (1% in the general population) and is 90% by age 70. Early onset breast cancer accounts for 25% of all the cancers in this syndrome. This is followed by soft tissue sarcomas (20%), bone sarcoma (15%) and brain tumors - especially glioblastomas - (13%). Other tumours seen in this syndrome include leukemia, lymphoma and adrenocortical carcinoma.

~90% of females with LFS develop breast cancer by age 60 years; the majority of these occur before age 45 years. Females with this syndrome have almost a 100% lifetime risk of developing cancer. This compares with 73% for affected males. The difference may be due to much smaller breast tissue in males as well as increased estrogen levels in females.

The risks of sarcoma, female breast cancer and haematopoietic malignancies in mutation carriers are more than 100 times greater than those seen in the general population.

Other tumours reported in this syndrome but not yet proved to be linked with it include melanoma, Wilm's and other kidney tumors, hepatacellular carcinoma, gonadal germ cell, pancreatic, gastric, choroid plexus, colorectal and prostate cancers.

80% of children with adrenocortical carcinoma and 2%-10% of childhood brain tumors have p53 mutations.

2%-3% of osteosarcomas, 9% rhabdomyosarcomas and 7%-20% patients with multiple primary tumors have p53 mutations.

Although most cases of this syndrome have early onset of cancer, cases have also been reported later in life.