To assess the impact of family history on the risk of developing breast cancer, a case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. In total, 1,551 breast cancer cases were included and 28,450 women, confirmed as free of cancer, were recruited as the reference group. The odds ratios (ORs) and their 95% confidence intervals (95% CIs) were estimated by using an unconditional logistic regression model. Stratification by age at diagnosis was done to evaluate the impact of family history on early (< 40 years of age) vs. later (> or = 40 years of age) onset. New findings obtained from the present study were as follows. 1) For women having a family member with ovarian cancer, the OR for breast center diagnosed under age 40 was 5.04 (95% CI: 1.48-17.1). 2) The effect of family history on the risk of breast cancer was greater when a sister(s) was (were) positive (OR = 3.51) than when the mother was positive (OR = 1.47). 3) The estimated proportional ratio (PR) for breast cancer was 2.63 (95% CI: 2.05-3.38) among sisters excluding probands, while PR for cancers other than breast cancer was 1.09 (95% CI: 0.94-1.27). This result suggested that a family history of breast cancer, especially among sisters, elevated the risk of developing breast cancer. Furthermore, when women had a sister(s) with breast cancer diagnosed prior to 40 years of age, their family history of breast cancer affected their risk of cancer of the breast and other organs.