A correlation between chemotherapy-induced necrosis and prognosis has been reported in Ewing sarcoma. To identify factors influencing histologic response data from 122 patients with Ewing sarcoma surgically treated were reviewed. Primary chemotherapy was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, actinomycin-D, and etoposide. Patients with complete necrosis or only scattered foci of viable tumor cells were good responders (GRs), the remaining patients poor responders (PRs). Age, sex, site and size of the tumor, fever at diagnosis, and lactate dehydrogenase level were clinical variables investigated. Mean age was 13.3+/-6 in GR and 18.1+/-9 in PR (P<0.0005); GR rate was 71% in patients<or=14 years, 39% in patients aged 15 to 18 years, and 26% in patient>18 years (P=0.003). Female were more likely to achieve a GR (F 64% vs. M 42%, P<0.02). After multivariate analysis sex and age retained statistical significance. Age and sex influence the histologic response in patients with Ewing sarcoma.