Forty-six patients with extremity soft-tissue sarcomas were treated with a mean of 4.4 cycles of preoperative adriamycin-based combination chemotherapy, followed by definitive local surgery and radiotherapy. All tumors were larger than 5 cm and of histologic type having significant risk of metastasis. Eighteen patients (40%) had an objective clinical response to the chemotherapy, while 27 patients (60%) did not respond. Patients with tumors responsive to chemotherapy had significantly improved overall survival (median 60 + months versus 32.7 months; p = 0.02), continuous disease-free survival (median 60 + months versus 15.1 months; p = 0.04), and distant metastasis-free survival (median 60+ months versus 28.5 months; p = 0.006) compared to the nonresponding patients. Tumor response to preoperative chemotherapy provides strong prognostic information and identifies a subgroup of patients most likely to benefit from chemotherapy.