The authors reviewed a series of 2311 primary breast cancers followed-up from 1 to 11 years after radical mastectomy. Twenty-eight simultaneous and 40 metachronous controlateral breast cancers were observed in the study period with an average annual incidence rate of 4.5%. Younger age and histologic evidence of lobular carcinoma at first cancer diagnosis was significantly associated with contralateral cancer, whereas first cancer stage did not seem to be a risk factor. Contralateral metachronous cancer significantly worsened the expected prognosis, which was not true for simultaneous bilateral cancers. The possible reasons for this negative prognostic influence of a second breast cancer and the role of preventive measures such as contralateral mastectomy are discussed. At the present time, an accurate annual clinico-mammographic follow-up seems to be a most advisable course of action.