OBJECTIVES: To evaluate the association between family history of breast cancer and breast cancer risk among Hispanic and non-Hispanic white (NHW) women. METHODS: Logistic regression models were used to compute unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using data collected from the 4-Corners Breast Cancer Study, a population-based case-control study of breast cancer conducted in the Southwest United States (3,074 NHW and 1,647 Hispanic women). RESULTS: The association between family history of breast cancer and early-onset breast cancer risk differs among NHW and Hispanic women. Among women <50 years old, having a family history of breast cancer was associated with a greater increase in risk among NHWs, with an OR of 2.34 (95% CI: 1.64-3.35) when compared to an OR of 1.32 (95% CI: 0.82-2.19) for Hispanics. This difference in risk was not observed among women 50 years and older, with an OR of 1.69 (95% CI: 1.34-2.13) for NHW and 1.47 (95% CI: 1.03-2.10) for Hispanics. CONCLUSIONS: Family history of breast cancer poses a greater risk for early-onset breast cancers among NHW when compared to Hispanic women and may reflect ethnic differences in certain predisposing genetic factors that promote breast cancer development.