Thirty-one women with stage III breast cancer were prospectively treated with two cycles of cyclophosphamide (Cytoxan), doxorubicin hydrochloride (Adriamycin), fluorouracil, and tamoxifen citrate followed by a simple mastectomy with level I axillary dissection. Postoperatively, four additional cycles of the combination chemotherapy alternating with three cycles of 1500 rad (15 Gy) to the chest wall and lymphatics were given. Seventy-seven percent of patients had a greater than 50% reduction in tumor size after the initial chemotherapy. No tumor size progressed during therapy, and a single patient remained inoperable. Pathologic findings revealed nine patients with only microscopic residual tumor. Nuclear vacuolization was present in 42.8% of tumor cells after chemotherapy vs 14.2% of cells before chemotherapy. The mean follow-up for the groups is 24.3 months. To date, nine patients have had recurrence with only one isolated local recurrence. This therapy is effective in reducing primary tumor size and allows a limited mastectomy to be done with minimal morbidity.