Patients with Ewing's sarcoma should be transferred to a comprehensive cancer center for evaluation and management when the diagnosis is suspected. Proper biopsy technique is essential to preserve all therapeutic options, including limb preservation surgery. In addition to conventional histologic examination, biopsy tissue must be obtained for molecular biology studies. Demonstration of the consistent chromosomal translocation associated with Ewing's sarcoma is essential for diagnosis, and the specific type of fusion transcript has prognostic implications. Treatment must be intimately coordinated among oncologist, surgeon, and radiation oncologist. Successful treatment requires systemic, multi-agent chemotherapy and local control. The primary tumor can be treated with surgery, radiation therapy, or a combination of the two. The choice of modality should be dictated by the age of the patient, location of the primary tumor, functional consequences of the intervention, and concern about late effects, especially secondary malignancy. Treatment of the patient who presents with clinically detectable metastatic disease or who relapses after initial therapy remains unsatisfactory and controversial.