ESFT is most common in the first and second decade but may affect persons from age 2 to 80. It primarily affects white and Hispanic young people and is extremely rare in individuals of African or Asian origin. The reason for this striking ethnic distribution is not known, although interethnic differences exist for certain alleles of one of the genes consistently disrupted in these neoplasms. The ratio of male to female is 3:2.

Tumours can develop in almost any bone and soft tissue. ESFT is found in the lower extremity more than the upper extremity, but any long tubular bone may be affected. The most common sites are the metaphysis and diaphysis of the femur followed by the tibia and humerus. Ewing's sarcoma can also arise in soft tissue (extra-skeletal).

The clinical presentation of Ewing's sarcoma includes pain and swelling of weeks or months duration. Erythema and warmth of the local area are sometimes seen. Pathologic fracture is not rare. Frequently there is an increase of serum lactic dehydrogenase (LDH). Increased leukocytosis, anemia and erythrocyte sedimentation rate (ESR) are occasionally seen.

The imaging presentation is often vary variable. The most frequent appearance is a permeative “moth-eaten” or “rotten-wood” poorly defined osteolysis. Radiologically, Ewing's sarcoma is often associated with a lamellated or "onion skin" periosteal reaction. This appearance is caused by splitting and thickening of the cortex by tumor cells. The lesion is usually lytic and central. Endosteal scalloping is often present. The "onion-skin" appearance is often followed with a "moth-eaten" or mottled appearance and extension into soft tissue. Bone marrow infiltration is not obvious on plain x-ray. While Ewing's sarcoma is usually lytic it may present as a sclerotic lesion with bone expansion. CT is helpful in defining bone destruction. MRI is essential to elucidate the soft tissue involvement because with TI-weighted images the tumor has low intensity compared to the normal high intensity of bone marrow. On:1 2 -weighted images the tumor is hyper intense compared to muscle. Ewing's sarcoma has increased uptake on bone scan.

Grossly, the tumor is gray to white in color and poorly demarcated. The consistency is soft and gray and sometimes semi-liquid especially after breaking through the cortex. Areas of hemorrhage and necrosis are common. The destruction is often greater on gross appearance than was visible on radiographs. Under the microscope, Ewing's sarcoma consists of densely packed uniform small cells in sheets without any matrix products (blue tumor). The cells have rather monotonous appearance with scant cytoplasm and poorly defined borders. The nuclei are two to three times as big as lymphocytes, round to oval  without prominent nucleoli. Glycogen is present within the cells causing a positive reaction to periodic acid-schiff (PAS) stain. Most Ewing's sarcomas are positive with HBA-71 or 013 antibodies which recognize the protein product of the myc 2 gene, CD99. A neural origin is supported by electron microscope findings of pseudorosettes. This is further supported by the common finding in Ewing's sarcoma and primitive neuroectodermal tumors of choline acetyltransferase. It is thought that Ewing's sarcoma with its few organelles is the poorly differentiated end of the spectrum of PNET. Neuroepithelioma is an example of well differentiated PNET and has neurosecretory granules and neuritic processes.

The genetic hallmark of ESFT is the translocation t(11:22)(q24;ql2), which led to the hybrid fusion product EWS/FLI-1 and accounts for 85% of the cases. In the other 10-15 % the translocation  t(21;22)(q22;q12), which led to the fusion product EWS/ERG, is observed.

ESFT is highly sensitive to chemotherapy and radiotherapy. Thus the treatment is based on a combination of  multi-drug chemotherapy (always), surgery (whenever feasible) and radiotherapy (alternative to surgery or associated to a less than wide or radical surgery).

Chemotherapy is given preoperatively and postoperatively and is used as a combination of at least four drugs, the most effective being cyclophosphamide, ifosfamide, adriamycin, vincristine, actinomycin-D, etoposide. The most employed regimens are vincristine, actinomycin-D, cyclophosphamide, adriamycin (VACA) or more intensive, vincristine, actinomycin-D, ifosfamide, adriamycin (VAIA) and etoposide.

Prior to the use of effective chometherapy the long term survival was less than 10%. Now, with multimodal treatment, the same figure is around 60-70%.

The tumor metastasizes to lungs and lymph nodes. Poor prognostic signs include increased age, large tumor volume and metastases at presentation.