All patients with locally advanced breast cancer receiving definitive irradiation (with or without surgery) at the Radiation Oncology Service, Ospedali Galliera, Genova, Italy, from 1969 through 1986, were retrospectively reviewed. Group A consisted of 187 patients, affected with stage III disease, who received radiation therapy after radical surgery. Irradiation of the chest wall and regional lymph node chains was accomplished with divergent tangential beams of Cobalt: the dose was calculated at the mid-plane of the tangential field separation and was 50Gy (2 Gy/day, 5 fractions/week), followed by additional 10-15 Gy boost to the scar. One hundred and five patients received combined hormonotherapy and/or chemotherapy. After a mean follow-up of 49+ months we observed 21 local recurrences (16 in metastatic patients); 64 patients developed only distant metastases. Actuarial survival at 5 years is 55%. Group B consisted of 36 inoperable patients who received definitive irradiation. Radiation therapy planning was very similar to that in group A, even though after 50 Gy the breast and the tumor area were boosted with restricted fields up to a total dose of 80-90 Gy. Fifteen patients received combined hormonotherapy and/or chemotherapy. At the end of the treatment overall response rate was 89%; actuarial survival at 5 years is 38%. Toxicity was generally mild and no death related to the treatment was observed. Our retrospective analysis confirms the importance of a multimodal approach to locally advanced breast cancer in order to free most patients from disease and to produce excellent local control, even though more randomized studies are necessary to improve the long-term survival of these patients.