Following diagnosis and histopathological analysis, the patient will usually undergo magnetic resonance imaging (MRI), ultrasonography, and a bone scan in order to determine the extent of local invasion and metastasis. Further investigational techniques may be necessary depending on tumor sites. A parameningeal presentation of RMS will often require a lumbar puncture to rule out metastasis to the meninges. A paratesticular presentation will often require an abdominal CT to rule out local lymph node involvement, and so on. Patient outcomes are most strongly tied to the extent of the disease, so it is important to map its presence in the body as soon as possible in order to decide on a treatment plan.

The current staging system for rhabdomyosarcoma is unusual relative to most cancers. It utilizes a modified TNM (tumor-nodes-metastasis) system originally developed by the IRSG. This system accounts for tumor size (> or <5 cm), lymph node involvement, tumor site, and presence of metastasis. It grades on a scale of 1 to 4 based on these criteria. In addition, patients are sorted by clinical group (from the clinical groups from the IRSG studies) based on the success of their first surgical resection. The current Children's Oncology Group protocols for the treatment of RMS categorize patients into one of four risk categories based on tumor grade and clinical group, and these risk categories have been shown to be highly predictive of outcome.

Rhabdomyosarcoma is often difficult to diagnose due to its similarities to other cancers and varying levels of differentiation. It is loosely classified as one of the “small, round, blue-cell cancer of childhood” due to its appearance on an H&E stain. Other cancers that share this classification include neuroblastoma, Ewing sarcoma, and lymphoma, and a diagnosis of RMS requires confident elimination of these morphologically similar diseases. The defining diagnostic trait for RMS is confirmation of malignant skeletal muscle differentiation with myogenesis (presenting as a plump, pink cytoplasm) under light microscopy. Cross striations may or may not be present. Accurate diagnosis is usually accomplished through immunohistochemical staining for muscle-specific proteins such as myogenin, muscle-specific actin, desmin, D-myosin, and myoD1. Myogenin, in particular, has been shown to be highly specific to RMS, although the diagnostic significance of each protein marker may vary depending on the type and location of the malignant cells. The alveolar type of RMS tends to have stronger muscle-specific protein staining. Electron microscopy may also aid in diagnosis, with the presence of actin and myosin or Z bands pointing to a positive diagnosis of RMS. Classification into types and subtypes is accomplished through further analysis of cellular morphology (alveolar spacings, presence of cambium layer, aneuploidy, etc.) as well as genetic sequencing of tumor cells. Some genetic markers, such as the "PAX3-FKHR" fusion gene expression in alveolar RMS, can aid in diagnosis. Open biopsy is usually required to obtain sufficient tissue for accurate diagnosis. All findings must be considered in context, as no one trait is a definitive indicator for RMS.

The disease used to be uniformly fatal, with a 5-year survival rate between 10 and 35%. As a result, treatment was radical surgery. New multidrug chemotherapy regimens with or without radiation therapy are now used in combination with less radical surgery with good results, although outcome data are not yet available.

Sarcoma botryoides normally is found in children under 8 years of age. Onset of symptoms occurs at age 3 years (38.3 months) on average. Cases of older women with this condition have also been reported.

NMC when viewed microscopically, are poorly differentiated carcinomas which show abrupt transitions to islands of well-differentiated squamous epithelium. This tumor pattern is not specific or unique to NUT midline carcinoma, but this pattern is most suggestive of the diagnosis. The neoplastic cells will show a positive reaction with various cytokeratins, p63, CEA, and CD34 immunohistochemistry. However, the NUT antibody confirms the diagnosis (although only available in a limited number of laboratories).

The differential diagnosis is quite wide, but it is important to consider this tumor type when seeing a poorly differentiated tumor that shows abrupt areas of keratinization. Other tumors included in the differential diagnosis are sinonasal undifferentiated carcinomas, Ewing sarcoma/Primitive neuroectodermal tumor, leukemia, rhabdomyosarcoma, and melanoma. When NUT midline carcinoma is seen in the head and neck, the squamous lining of the cavities may be entrapped by the neoplastic cells, and so it is important to document the carcinoma cells in the rest of the tumor by a variety of stains (including cytokeratin or p63). One of the most helpful and characteristic findings is the focal abrupt squamous differentiation, where stratification and gradual differentiation are absent, resembling a Hassall corpuscle of the thymus.

The defining feature of NMCs is rearrangement of the "NUT" gene.

Most common is a translocation involving the BRD4 gene and NUT gene (t(15;19)(q13;p13.1)).

Regardless of location, all rhabdoid tumours are highly aggressive, have a poor prognosis, and tend to occur in children less than two years of age.

DSRCT is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.

There is no standard protocol for the disease; however, recent journals and studies have reported that some patients respond to high-dose (P6 Protocol) chemotherapy, maintenance chemotherapy, debulking operation, cytoreductive surgery, and radiation therapy. Other treatment options include: hematopoietic stem cell transplantation, intensity-modulated radiation Therapy, radiofrequency ablation, stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.

Because this is a rare tumor, not many family physicians or oncologists are familiar with this disease. DSRCT in young patients can be mistaken for other abdominal tumors including rhabdomyosarcoma, neuroblastoma, and mesenteric carcinoid. In older patients DSRCT can resemble lymphoma, peritoneal mesothelioma, and peritoneal carcinomatosis. In males DSRCT may be mistaken for germ cell or testicular cancer while in females DSRCT can be mistaken for Ovarian cancer. DSRCT shares characteristics with other small-round blue cell cancers including Ewing's sarcoma, acute leukemia, small cell mesothelioma, neuroblastoma, primitive neuroectodermal tumor, rhabdomyosarcoma, and Wilms' tumor.

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

Anal Pap smears similar to those used in cervical cancer screening have been studied for early detection of anal cancer in high-risk individuals. In 2011, the HIV clinic implemented a program to enhance access to anal cancer screening for HIV-positive men. Nurse practitioners perform anal Papanicolaou screening, and men with abnormal results receive further evaluation with high-resolution anoscopy. The program has helped identify many precancerous growths, allowing them to be safely removed.

Diagnostic tests typically include complete blood tests, urinalysis, urine culture, X-rays of the abdomen and chest, and bladder imaging. The definitive diagnosis of bladder cancer will require a tissue biopsy and subsequent examination of the cells under the microscope.

A 2009 revision of the traditional Chompret criteria for screening has been proposed:

A proband who has:

- tumor belonging to the LFS tumor spectrum - soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumor, adrenocortical carcinoma, leukemia or lung bronchoalveolar cancer - before age 46 years;

and at least one of the following:

- at least one first or second degree relative with an LFS tumour (except breast cancer if the proband has breast cancer) before age 56 years or with multiple tumours

- a proband with multiple tumours (except multiple breast tumours), two of which belong to the LFS tumour spectrum and the first of which occurred before age 46 years

- a proband who is diagnosed with adrenocortical carcinoma or choroid plexus tumour, irrespective of family history

Patients who have been diagnosed with ARMS often have poor outcomes. The four year survival rate without remission for local ARMS tumors is 65 percent, while the four year survival rate with metastatic ARMS is only 15 percent. Patients who have metastatic ARMS positive with PAX3-FOXO1 fusion often have a poorer outcome than patients positive with PAX7-FOXO1 fusion, with a four-year survival rate of 8 percent and 75 percent respectively. Other variables affect the four year survival rate, such as, primary tumor site, size of primary tumor, amount of local invasion, number of distal lymph nodes spread to, and whether metastasis has occurred. Prognosis for patients who have primary tumor sites within the bones often have higher survival rates and respond well to treatment options. While patients who have primary tumor sites within the nasopharynx region with metastases to the breast have very poor outcomes. Patients who are fusion protein negative with low risk clinical features should be treated with reduced therapy, while patients who are fusion protein positive with low risk clinical features should be treated as an intermediate risk and have more intensive therapy regimens.

The symptoms of childhood rhabdomyosarcoma are visible and prominent and include swollen red lumps where the cancer starts developing. The lumps are hard and can grow in size unless treated. Other symptoms include poor bowel movements, blood in the urine, secretions from the genitals and nose, and headaches. Various tests can determine whether these related symptoms indicate childhood rhabdomyosarcoma. CT, X-ray, MRI, bone scans, and Ultrasounds may be performed to identify the location and size of the cancer. Biopsies of the lump can be taken along with bone marrow biopsies to detect whether the cancer has spread within the marrow, the bone, and the blood supply. Further determination of how aggressive and large the cancer is requires these scans.

Genetic counseling and genetic testing are used to confirm that somebody has this gene mutation. Once such a person is identified, early and regular screenings for cancer are recommended for him or her as people with Li–Fraumeni are likely to develop another primary malignancy at a future time (57% within 30 years of diagnosis).

Surgery is important in the treatment of most sarcomas. Limb sparing surgery, as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity tumor cases. Additional treatments, including chemotherapy and radiation therapy, may be administered before and/or after surgery. Chemotherapy significantly improves the prognosis for many sarcoma patients, especially those with bone sarcomas. Treatment can be a long and arduous process, lasting about a year for many patients.

- Liposarcoma treatment consists of surgical resection, with chemotherapy not being used outside of the investigative setting. Adjuvant radiotherapy may also be used after surgical excision for liposarcoma.

- Rhabdomyosarcoma is treated with surgery, radiotherapy, and/or chemotherapy. The majority of rhabdomyosarcoma patients have a 50–85% survival rate.

- Osteosarcoma is treated with surgical resection of as much of the cancer as possible, often along with neoadjuvant chemotherapy. Radiotherapy is a second alternative although not as successful.

NUT midline carcinoma is very resistant to standard chemotherapy treatments. The tumor may initially respond to therapy, and then rapid recurrence is experienced, followed by death. A multimodality approach to treatment is advocated, especially since most patients present with advanced disease. Treatment must be tailored to the individual patient, with several promising new targeted molecular therapies in clinical trials. Specific molecular targeted therapies (BET inhibitors and histone deacetylase inhibitors (HDACi)) may help to yield growth arrest of the neoplastic cells. Overall, there is a mean survival of 6–9 months.

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.

Because most bladder cancers are invasive into the bladder wall, surgical removal is usually not possible. The majority of transitional cell carcinomas are treated with either traditional chemotherapy or nonsteroidal anti-inflammatory drugs.

The histologic diagnosis of malignant rhabdoid tumour depends on identification of characteristic rhabdoid cells—large cells with eccentrically located nuclei and abundant, eosinophilic cytoplasm. However, the histology can be heterogeneous and the diagnosis of MRT can often be difficult. Misclassifications can occur.

In MRTs, the INI1 gene (SMARCB1)on chromosome 22q functions as a classic tumour suppressor gene. Inactivation of INI1 can occur via deletion, mutation, or acquired UPD.

In a recent study, SNP array karyotyping identified deletions or LOH of 22q in 49/51 rhabdoid tumours. Of these, 14 were copy neutral LOH (or acquired UPD), which is detectable by SNP array karyotyping, but not by FISH, cytogenetics, or arrayCGH. MLPA detected a single exon homozygous deletion in one sample that was below the resolution of the SNP array. SNP array karyotyping can be used to distinguish, for example, a medulloblastoma with an isochromosome 17q from a primary rhabdoid tumour with loss of 22q11.2. When indicated, molecular analysis of INI1 using MLPA and direct sequencing may then be employed. Once the tumour-associated changes are found, an analysis of germline DNA from the patient and the parents can be done to rule out an inherited or de novo germline mutation or deletion of INI1, so that appropriate recurrence risk assessments can be made.

Since many, if not most, anal cancers derive from HPV infections, and since the HPV vaccine before exposure to HPV prevents infection by some strains of the virus and has been shown to reduce the incidence of potentially precancerous lesions, scientists surmise that HPV vaccination may reduce the incidence of anal cancer.

On 22 December 2010, the U.S. Food and Drug Administration approved Gardasil vaccine to prevent anal cancer and pre-cancerous lesions in males and females aged 9 to 26 years. The vaccine has been used before to help prevent cervical, vulvar, and vaginal cancer, and associated lesions caused by HPV types 6, 11, 16, and 18 in women.

ARMS usually occurs in the skeletal muscle tissue of the extremities, but it is still very common in the torso, head, and neck regions. The primary tumor often presents itself as a soft mass of tissue that is painless, but the tumor can be detected if it starts to put pressure on other structures in the primary site. A large fraction of patients who are diagnosed with ARMS, roughly 25-30 percent, will have metastases at the time of diagnosis. The standard sites for metastases to form are the bone marrow, the bones, and distal nodes. Typical treatment options for patients who have been diagnosed with ARMS include standard surgery, radiation therapy, and intensive chemotherapy.

Anal sac adenocarcinomas are often suspected due to location (palpable masse in anal sac) and behavior, but a biopsy and histopathology is necessary for a definitive diagnosis. Fine needle aspiration and cytology is a common first step. Cytopathology reveals clusters of cells with uniform round nuclei. These cells do not have many of the features usually associated with malignancy, such as a high nucleus to cytoplasm ratio or prominent nucleoli. Ultrasonography and radiography are performed to look for metastasis.

Childhood rhabdomyosarcoma has been fatal. Recovery rates have increased by 50 percent since 1975. In children five years of age or younger survival rates are up to 65 percent. In adolescents younger than 15 years old, the survival rate has increased up to 30 percent.

Aggressive surgical removal of the tumor and any enlarged sublumbar lymph nodes is essential for treatment of the tumor and associated hypercalcaemia. There is a high recurrence rate, although removal of lymph nodes with metastasis may improve survival time. Radiation therapy and chemotherapy may be helpful in treatment. Severe hypercalcaemia is treated with aggressive IV fluid therapy using sodium chloride and medications such as loop diuretics (increased kidney excretion of calcium) and aminobisphosphonates (decreased calcium release from bones). A poorer prognosis is associated with large tumor size (greater than 10 cm), hypercalcaemia, and distante metastasis. Early, incidental diagnosis of small anal sac masses may lead to a better prognosis with surgery alone (ongoing study).