The nation-wide Swedish Family-Cancer Database was used to analyze the risk of contralateral breast cancer among 72,092 women with unilateral breast cancer. Contralateral breast cancer, defined as being diagnosed 6 months or more after the first breast cancer, affected 2,529 women (3.5%). In a young age group the incidence of contralateral breast cancer was 50 times higher than the incidence of first breast cancer; for all contralateral breast cancer the difference was 5-fold. Because only 1 breast was at risk for contralateral breast cancer, the true differences to unilateral cancer were 2 times higher. The age-incidence relationship was unusual, exhibiting a high incidence (800/10(5) person-years) component at an early age (25 to 49 years) and a lower incidence (460/10(5) person-years) component at a later age (50-80 years). The discrete components suggest population heterogeneity. Age at diagnosis of the first breast cancer and family history of breast cancer associated with the risk of contralateral breast cancer. Other, weaker risk factors were birth cohort, age at first childbirth, parity and interval between first and second breast cancer. The incidence of familial contralateral breast cancer was 1. 5 times higher than that of sporadic disease, and its age-incidence curve also exhibited 2 separate components. The age-incidence relationships of contralateral breast cancer suggest that the disease affects a small and heterogeneous susceptible population.