Neoadjuvant chemotherapy (NC) has been shown to reduce primary breast tumor size in 80 to 90 per cent of patients. This study prospectively evaluated a series of women with locally advanced operable breast cancer treated with NC with the purpose of identifying eligibility for breast conservation surgery (BC) and clinical parameters predictive of chemotherapy response. Patients with stage IIB and III primary operable breast cancer were evaluated prospectively between 1/1/91 and 12/31/95. Thirty-two patients received NC consisting of three cycles of 5-fluorouracil, doxirubicin, and cyclophosphamide. Prechemotherapy tumor size was assessed by palpation and mammography. Patients were offered BC depending on clinical response. Initial tumor size averaged 7 cm (range, 4-15 cm). Reduction of > 50 per cent in tumor size occurred in 17 patients (53%). Twenty-one patients (66%) were potential candidates for BC based on a post-NC pathologic tumor size of less than 4 cm. Five patients (16%) had no residual breast tumor. Four patients underwent BC (13%). Partial response was not associated with patients age, menopausal status, tumor steroid receptor or Her-2/NEU positivity, or tumor size. Patients with a clinically negative axilla had a higher likelihood of partial or complete response. NC in patients with locally advanced breast disease has a high response rate (88%) and can significantly reduce tumor size to enable conservation of the breast.