The records of 116 patients from a single center (1970-1993) with newly diagnosed Ewing's sarcoma or primitive neuroectodermal tumor were reviewed retrospectively. The aim of this study was to ascertain the impact of pretreatment variables on disease-free survival. Median age was 14 years (range 1-34). Twenty patients presented with metastatic disease. Treatment consisted of systemic multiagent chemotherapy plus local irradiation (39%), wide resection (22%), or both (35%). Median potential follow-up was 10.7 years (range 2-26). Three patients developed second malignancies (1 breast carcinoma, 2 acute myeloid leukemias). Median time to relapse was 24 months (range 3-143). The actuarial disease-free survival was 37.4% at 5 years, 33.3% at 10 years and 27.8% at 15 years. Neoadjuvant chemotherapy and a therapy-induced tumor necrosis > or = 90% were associated with a better outcome. Patients undergoing surgical resection had a superior disease-free survival than those treated without surgery (45 vs. 18% at 10 years, p = 0.0009). Multiple regression analysis showed that raised serum lactate dehydrogenase levels (p < 0.001), hypoalbuminemia (p = 0.001) and distant metastases at diagnosis (p = 0.03) were independent adverse prognostic factors. In conclusion, one third of patients with Ewing's sarcoma become long-term survivors with combined modality treatment. Late relapses and second neoplasms are of concern. Prognostic factors should be considered in the selection of therapy, and the value of serum albumin warrants confirmatory studies.