Locally advanced breast cancer has been treated with a variety of primary treatments with or without adjuvant therapies. This study combines radiation, chemotherapy, and surgery as a multimodal program for Stage III breast cancer. Radiation was started on day 1: 4600 rad were administered to the breast and 4500 rad were administered to the axilla and supraclavicular areas. Chemotherapy was started on day 1 with weekly intravenous injections of 5-fluorouracil (5FU) (300 mg/m2), methotrexate (15 mg/m2), vincristine (0.625 mg/m2), oral cytoxan (60 mg/m2), and prednisone (30 mg/m2 for two weeks, then 20 mg/m2 for two weeks, then 10 mg/m2 for two weeks). The 5FU, methotrexate, and cytoxan were given for 10 months postsurgery. This combination of modalities produced a complete remission in all 13 patients with Stage III breast cancer after two months of therapy. The median disease-free period was two years. The median survival was 44 months. This approach to the management of Stage III breast cancer is worthy of further investigation.