The association between passive cigarette smoke exposure and breast cancer risk is inconclusive and may be modified by genotype. The authors investigated lifetime passive cigarette smoke exposures, 36 variants in 12 carcinogen-metabolizing genes, and breast cancer risk among Ontario, Canada, women who had never smoked (2003-2004). DNA (saliva) was available for 920 breast cancer cases and 960 controls. Detailed information about passive smoke exposure was collected for multiple age periods (childhood, teenage years, and adulthood) and environments (home, work, and social). Adjusted odds ratios and 95% confidence intervals were estimated by multivariable logistic regression, and statistical interactions were assessed using the likelihood ratio test. Among postmenopausal women, most associations between passive smoke and breast cancer risk were null, whereas among premenopausal women, nonsignificant positive associations were observed. Significant interactions were observed between certain types of passive smoke exposure and genetic variants in CYP2E1, NAT2, and UGT1A7. While these interactions were statistically significant, the magnitudes of the effect estimates were not consistent or easily interpretable, suggesting that they were perhaps due to chance. Although the results of this study were largely null, it is possible that premenopausal women exposed to passive smoke or carrying certain genetic variants may be at higher risk of breast cancer.