Breast cancer risk may be influenced by intrauterine exposure to steroid hormones. We evaluated left-handedness, a marker of intrauterine hormone exposure, in relation to breast cancer risk in our population-based, case-control study. Case women 50-79 years of age with a first diagnosis of invasive breast cancer were ascertained through statewide cancer registries in Wisconsin, Massachusetts, and New Hampshire. Control women were identified in each state through lists of licensed drivers (for ages 50-64) and Medicare beneficiaries (for ages 65-79), and selected at random to correspond with the age distribution of case women. Exposure information, including handedness, was obtained through a telephone interview. Our results indicated a modest association between left-handedness and breast cancer risk (OR = 1.42; 95% CI = 1.10-1.83). The effect of left-handedness was modified by age; we observed the greatest risk ratio in the oldest age group. Left-handedness was not associated with breast tumor laterality. Our results are consistent with the hypothesis that intrauterine hormone exposures play a role in the development of breast cancer.