This epidemiologic investigation comprised 1351 of 1423 women in a defined geographic area consecutively diagnosed as having a primary breast cancer. Simultaneous bilateral disease occurred in only 1 patient, whereas a history of previous cancer in the contralateral breast was reported by 65 patients. This prevalence was related to that of 23 previous cases in an age-matched control group of 1351 women from the same population. The relative risk of developing a second primary was 2.9 (95% confidence limit, 1.8-4.6) for the whole material and remained seemingly constant over several decades at a level predetermined by age at first diagnosis, namely 9.9 (95% confidence limit, 3.8-25.8) before the age of 50 and 1.9 (95% confidence limit, 1.1-3.2) after that age. The incidence ratio of bilateral to unilateral disease was used as an estimate of the lifetime risk of developing a second primary in this stable and well-defined population. This calculation revealed cumulative risk figures of 13.3% and 3.5% for women younger and older than 50 years, respectively, at first diagnosis. It was concluded that the occurrence of bilateral disease, which reflects a multicentric neoplastic transformation of the breast epithelium, is a characteristic of early-occurring (premenopausal) disease.