This case control study investigated whether polymorphisms of estrogen metabolizing genes CYP1A1 MspI, CYP17 MspAI, COMT Val(158) Met, and SULT1A1 Arg(213) His have any role in familial breast cancer susceptibility risk. Logistic regression analysis adjusted to age was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs). Familial breast cancer risk due to CYP1A1 wt/m1 and m1/m1 genotypes was 2.3 (1.51-3.61)-fold and 7.1 (3.69-13.7)-fold, respectively. In addition to the main effects, certain first-order interactions were also significantly associated with familial breast cancer. Our results favor a possible risk modification by estrogen metabolizing gene polymorphisms in familial breast cancer susceptibility.