PURPOSE: The identification of prognostic factors in patients with nonmetastatic Ewing’s sarcoma could allow the use of risk-adapted therapeutic strategies of treatment. PATIENTS AND METHODS: Data on 359 patients with nonmetastatic Ewing’s sarcoma of bone treated at a single institution between January 1979 and April 1995 were retrospectively considered. The influence of clinical, hematologic, therapeutic, and histologic parameters on event-free survival was assessed. RESULTS: By univariate analysis, the following features were found to be associated with a poor prognosis: male sex (P < .02), age older than 12 years (P < .006), fever (P < .0001), anemia (P < .0025), high serum lactate dehydrogenase (LDH) level (P < .0001), axial location (P < .04), radiation therapy only for local control (P < .009), type of chemotherapy regimen (P < .0001), and poor chemotherapy-induced necrosis (P < .001). After multivariate analysis, the adverse independent prognostic factors were male sex (P < .04), age older than 12 years (P < .001), fever (P < .0002), anemia (P < .02), high serum LDH level (P < .0003), axial location (P < .02), and type of chemotherapy regimen (P < .0003). When the multivariate analysis was restricted to surgically treated patients, the adverse independent prognostic factors were poor chemotherapy-induced necrosis (P < .0001), fever (P < .015), anemia (P < .02), and high serum LDH level (P < .025). CONCLUSION: The prognosis in cases of nonmetastatic Ewing’s sarcoma is influenced by many different clinical and hematologic variables, all of which are to be considered when patients are being stratified according to the risk of relapse. In surgically treated patients, the most important prognostic factor is chemotherapy-induced necrosis.