Prognosis is separated into three groups.

- Stage I osteosarcoma is rare and includes parosteal osteosarcoma or low-grade central osteosarcoma. It has an excellent prognosis (>90%) with wide resection.

- Stage II prognosis depends on the site of the tumor (proximal tibia, femur, pelvis, etc.), size of the tumor mass, and the degree of necrosis from neoadjuvant chemotherapy. Other pathological factors such as the degree of p-glycoprotein, whether the tumor is cxcr4-positive, or Her2-positive are also important, as these are associated with distant metastases to the lung. The prognosis for patients with metastatic osteosarcoma improves with longer times to metastases, (more than 12 months to 4 months), a smaller number of metastases, and their resectability. It is better to have fewer metastases than longer time to metastases. Those with a longer length of time (more than 24 months) and few nodules (two or fewer) have the best prognosis, with a two-year survival after the metastases of 50%, five-year of 40%, and 10-year of 20%. If metastases are both local and regional, the prognosis is worse.

- Initial presentation of stage III osteosarcoma with lung metastases depends on the resectability of the primary tumor and lung nodules, degree of necrosis of the primary tumor, and maybe the number of metastases. Overall survival prognosis is about 30%.

Deaths due to malignant neoplasms of the bones and joints account for an unknown number of childhood cancer deaths. Mortality rates due to osteosarcoma have been declining at about 1.3% per year. Long-term survival probabilities for osteosarcoma have improved dramatically during the late 20th century and approximated 68% in 2009.

Several research groups are investigating cancer stem cells and their potential to cause tumors along with genes and proteins causative in different phenotypes.Radiotherapy for unrelated conditions may be a rare cause.

- Familial cases where the deletion of chromosome 13q14 inactivates the retinoblastoma gene is associated with a high risk of osteosarcoma development.

- Bone dysplasias, including Paget's disease of bone, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses, increase the risk of osteosarcoma.

- Li–Fraumeni syndrome (germline TP53 mutation) is a predisposing factor for osteosarcoma development.

- Rothmund–Thomson syndrome (i.e. autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts) is associated with increased risk of this disease.

- Large doses of Sr-90 emission from nuclear reactor, nicknamed bone seeker increases the risk of bone cancer and leukemia in animals, and is presumed to do so in people.

Despite persistent rumors suggesting otherwise, there is no clear association between water fluoridation and cancer or deaths due to cancer, both for cancer in general and also specifically for bone cancer and osteosarcoma. Series of research concluded that concentration of fluoride in water doesn't associate with osteosarcoma. The beliefs regarding association of fluoride exposure and osteosarcoma stem from a study of US National Toxicology program in 1990, which showed uncertain evidence of association of fluoride and osteosarcoma in male rats. But there is still no solid evidence of cancer-causing tendency of fluoride in mice. Fluoridation of water has been practiced around the world to improve citizens' dental health. It is also deemed as major health success. Fluoride concentration levels in water supplies are regulated, such as United States Environmental Protection Agency regulates fluoride levels to not be greater than 4 milligrams per liter. Actually, water supplies already have natural occurring fluoride, but many communities chose to add more fluoride to the point that it can reduce tooth decay. Fluoride is also known for its ability to cause new bone formation. Yet, further research shows no osteosarcoma risks from fluoridated water in humans. Most of the research involved counting number of osteosarcoma patients cases in particular areas which has difference concentrations of fluoride in drinking water. The statistic analysis of the data shows no significant difference in occurrences of osteosarcoma cases in different fluoridated regions. Another important research involved collecting bone samples from osteosarcoma patients to measure fluoride concentration and compare them to bone samples of newly diagnosed malignant bone tumors. The result is that the median fluoride concentrations in bone samples of osteosarcoma patients and tumor controls are not significantly different. Not only fluoride concentration in bones, Fluoride exposures of osteosarcoma patients are also proven to be not significantly different from healthy people.

Giant-cell tumor of the bone accounts for 4-5% of primary bone tumors and about 20% of benign bone tumors. However, significantly higher incidence rates are observed in Asia, where it constitutes about 20% of all primary bone tumors in China. It is slightly more common in females, has a predilection for the epiphyseal/metaphyseal region of long bones, and generally occurs in the third to fourth decade. Although classified as a benign tumor, GCTOB has been observed to metastesize to the lungs in up to 5% of cases, and in rare instances (1-3%) can transform to the malignant sarcoma phenotype with equal disease outcome.

Fibrosarcoma occurs most frequently in the mouth in dogs . The tumor is locally invasive, and often recurs following surgery . Radiation therapy and chemotherapy are also used in treatment. Fibrosarcoma is also a rare bone tumor in dogs.

In cats, fibrosarcoma occurs on the skin. It is also the most common vaccine-associated sarcoma. In 2014, Merial launched Oncept IL-2 in Europe for the management of such feline fibrosarcomas.

Ewing's sarcomas represent 16% of primary bone sarcomas. In the United States, they are most common in the second decade of life, with a rate of 0.3 cases per million in children under 3 years of age, and as high as 4.6 cases per million in adolescents aged 15–19 years. Internationally, the annual incidence rate averages less than 2 cases per million children. In the United Kingdom, an average of six children per year are diagnosed, mainly males in early stages of puberty. Due to the prevalence of diagnosis during teenage years, a link may exist between the onset of puberty and the early stages of this disease, although no research confirms this hypothesis.

The oldest known patient diagnosed was at age 76, from the Mercer County, New Jersey, area.

A grouping of three unrelated teenagers in Wake Forest, NC, have been diagnosed with Ewing's sarcoma. All three children were diagnosed in 2011 and all attended the same temporary classroom together while the school underwent renovation. A fourth teenager living nearby was diagnosed in 2009. The odds of this grouping are considered significant.

Ewing's sarcoma shows striking differences in incidence across human populations and is about 10- to 20-fold more common in populations from European descent as compared to Africans. Consistently, a genome-wide association study (GWAS) conducted in several hundreds European individuals with Ewing's sarcoma and genetically-matched healthy controls identified three susceptibility loci located on chromosomes 1, 10 and 15. A continuative study discovered that the Ewing's sarcoma susceptibility gene "EGR2", which is located within the chromosome 10 susceptibility locus, is regulated by the "EWSR1-FLI1" fusion oncogene via a GGAA-microsatellite.

Ewing's sarcoma is the second most common bone cancer in children and adolescents, with poor prognosis and outcome in ~70% of initial diagnoses and 10–15% of relapses.

ASPS is an extremely rare cancer. While sarcomas comprise about 1% of all newly diagnosed cancers, and 15% of all childhood cancers, ASPS comprises less than 1% of sarcomas. According to the American Cancer Society, about 9530 new cases of soft tissue sarcoma will be diagnosed in the USA in 2006. This predicts under 100 new cases of ASPS. Such low numbers of occurrence seriously impede the search for a cure by making it hard to gather any meaningful statistics about the disease. As a result, finding the best treatment option often involves making a lot of educated guesses.

A number of tumors have giant cells, but are not true benign giant-cell tumors. These include, aneurysmal bone cyst, chondroblastoma, simple bone cyst, osteoid osteoma, osteoblastoma, osteosarcoma, giant-cell reparative granuloma, and brown tumor of hyperparathyroidism.

Individuals presenting with fibrosarcoma are usually adults aged thirty to fifty five years, often presenting with pain. In adults, males have a higher incidence for fibrosarcoma than females.

Work out of Huntsman Cancer Institute (HCI) in Utah has demonstrated that ASPS might be driven in part by lactate both being used as a fuel and driving angiogenesis.

Staging attempts to distinguish patients with localized from those with metastatic disease. Most commonly, metastases occur in the chest, bone and/or bone marrow. Less common sites include the central nervous system and lymph nodes.

Five-year survival for localized disease is 70% to 80% when treated with chemotherapy. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. However, some sources state it is 25–30%.

Retrospective research in patients led by Idriss M. Bennani-Baiti (Cancer Epigenetics Society) showed that two chemokine receptors, CXCR4 and CXCR7, can be used as molecular prognosis factors. Patients who express low levels of both chemokine receptors have the highest odds of long-term survival with >90% survival at 5 years post-diagnosis versus <30% survival at 5 years for patients with very high expression levels of both receptors.

Most soft-tissue sarcomas are not associated with any known risk factors or identifiable cause. There are some exceptions:

- Studies suggest that workers who are exposed to chlorophenols in wood preservatives and phenoxy herbicides may have an increased risk of developing soft-tissue sarcomas. An unusual percentage of patients with a rare blood vessel tumor, angiosarcoma of the liver, have been exposed to vinyl chloride in their work. This substance is used in the manufacture of certain plastics, notably PVC.

- In the early 1900s, when scientists were just discovering the potential uses of radiation to treat disease, little was known about safe dosage levels and precise methods of delivery. At that time, radiation was used to treat a variety of noncancerous medical problems, including enlargement of the tonsils, adenoids, and thymus gland. Later, researchers found that high doses of radiation caused soft-tissue sarcomas in some patients. Because of this risk, radiation treatment for cancer is now planned to ensure that the maximum dosage of radiation is delivered to diseased tissue while surrounding healthy tissue is protected as much as possible.

- Kaposi's sarcoma, a rare cancer of the cells that line blood vessels in the skin and mucus membranes, is caused by Human herpesvirus 8. Kaposi's sarcoma often occurs in patients with AIDS (acquired immune deficiency syndrome). Kaposi's sarcoma, however, has different characteristics than typical soft-tissue sarcomas and is treated differently.

- In a very small fraction of cases, sarcoma may be related to a rare inherited genetic alteration of the p53 gene and is known as Li-Fraumeni syndrome. Certain other inherited diseases are associated with an increased risk of developing soft-tissue sarcomas. For example, people with neurofibromatosis type I (also called von Recklinghausen's disease, associated with alterations in the NF1 gene) are at an increased risk of developing soft-tissue sarcomas known as malignant peripheral nerve sheath tumors. Patients with inherited retinoblastoma have alterations in the RB1 gene, a tumor suppressor gene, and are likely to develop soft-tissue sarcomas as they mature into adulthood.

Undifferentiated pleomorphic sarcoma is regarded as the most common soft tissue sarcoma of late adult life. It rarely occurs in children. It occurs more often in Caucasians than in those of African or Asian descent and is a male-predominant disease, afflicting two males for every female.

Sarcomas are quite rare with only 15,000 new cases per year in the United States. Sarcomas therefore represent about one percent of the 1.5 million new cancer diagnoses in that country each year.

Sarcomas affect people of all ages. Approximately 50% of bone sarcomas and 20% of soft tissue sarcomas are diagnosed in people under the age of 35. Some sarcomas, such as leiomyosarcoma, chondrosarcoma, and gastrointestinal stromal tumor (GIST), are more common in adults than in children. Most high-grade bone sarcomas, including Ewing's sarcoma and osteosarcoma, are much more common in children and young adults.

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

Soft-tissue sarcomas are relatively uncommon cancers. They account for less than 1% of all new cancer cases each year. This may be because cells in soft tissue, in contrast to tissues that more commonly give rise to malignancies, are not continuously dividing cells.

In 2006, about 9,500 new cases were diagnosed in the United States. Soft-tissue sarcomas are more commonly found in older patients (>50 years old) although in children and adolescents under age 20, certain histologies are common (rhabdomyosarcoma, synovial sarcoma).

Around 3,300 people were diagnosed with soft tissue sarcoma in the UK 2011.

Prognosis depends on the primary tumor grade (appearance under the microscope as judged by a pathologist), size, resectability (whether it can be completely removed surgically), and presence of metastases. The five-year survival is 80%.

Embryonal rhabdomyosarcoma (ERMS) is a rare histological form of cancer of connective tissue wherein the mesenchymally-derived malignant cells resemble the primitive developing skeletal muscle of the embryo. It is the most common soft tissue sarcoma occurring in children.

A synovial sarcoma (also known as: malignant synovioma) is a rare form of cancer which occurs primarily in the extremities of the arms or legs, often in close proximity to joint capsules and tendon sheaths. As one of the soft tissue sarcomas, it is one of the rarest forms of soft tissue cancer.

The name "synovial sarcoma" was coined early in the 20th century, as some researchers thought that the microscopic similarity of some tumors to synovium, and its propensity to arise adjacent to joints, indicated a synovial origin; however, the actual cells from which the tumor develops are unknown and not necessarily synovial.

Primary synovial sarcomas are most common in the soft tissue near the large joints of the arm and leg but have been documented in most human tissues and organs, including the brain, prostate, and heart.

Synovial sarcoma occurs most commonly in the young, representing

about 8% of all soft tissue sarcomas but about 15–20% of cases occur in adolescents and young adults. The peak of incidence is in the third decade of life, with males being affected more often than females (ratio around 1.2:1).

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.

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.

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.

Synovial sarcoma usually presents with an otherwise asymptomatic swelling or mass, although general symptoms related to malignancies can be reported such as fatigue.

A hemangiopericytoma (HPC) is a type of soft tissue sarcoma that originates in the pericytes in the walls of capillaries. When inside the nervous system, although not strictly a meningioma tumor, it is a meningeal tumor with a special aggressive behavior. It was first characterized in 1942.

Dermatofibrosarcoma protuberans (DFSP)

is a very rare tumor. It is a rare neoplasm of the dermis layer of the skin, and is classified as a sarcoma. There is only about one case per million per year. DFSP is a fibrosarcoma, more precisely a cutaneous soft tissue sarcoma. In many respects, the disease behaves as a benign tumor, but in 2–5% of cases it can metastasize, so it should be considered to have malignant potential. It occurs most often in adults in their thirties; it has been described congenitally, in children, and the elderly. It accounts for approximately 2–6% of soft tissue sarcoma cancers.

Mast cell sarcoma is an extremely aggressive form of sarcoma made up of neoplastic mast cells. A sarcoma is a tumor made of cells from connective tissue. Mast cell sarcoma is an extremely rare tumor. Only 3 cases are reported so far. Prognosis is extremely poor. People with a mast cell sarcoma have no skin lesions, and pathology examination of the tumor shows it to be very malignant with an aggressive growth pattern. Mast cell sarcoma should not be confused with

extracutaneous mastocytoma, a rare benign mast cell tumor without destructive growth. In the cases observed, mast cell sarcoma terminated quickly as mast cell leukemia; one of the most aggressive human cancers.