BACKGROUND: Pathologic differences have been reported among breast tumors when comparing ethnic populations. Limited research has been done to evaluate the ethnic-specific relationships between breast cancer risk factors and the pathologic features of breast tumors. METHODS: Given that genetic variation may contribute to ethnic-related etiologic differences in breast cancer, we hypothesized that tumor characteristics differ according to family history of breast cancer among Hispanic and non-Hispanic White (NHW) women. Logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (95% CI) to assess this relationship in the population-based, case-control 4-Corners Breast Cancer Study (1,537 cases and 2,452 controls). RESULTS: Among Hispanic women, having a family history was associated with a 2.7-fold increased risk of estrogen receptor (ER) negative (95% CI, 1.59-4.44), but not ER positive tumors (OR, 1.04; 95% CI, 0.71-1.54) when compared with women without breast cancer. In contrast, there was an increased risk for ER positive (OR, 1.89; 95% CI, 1.50-2.38) and a marginally significant increased risk for ER negative tumors (OR, 1.41; 95% CI, 0.92-2.17) among NHW women. When comparing tumor characteristics among invasive cases, those with a family history also had a significantly higher proportion of ER negative tumors among Hispanics (39.2% versus 25.8%; P=0.02), but not among NHWs (16.3% versus 21.1%; P=0.13). CONCLUSIONS: These results may reflect ethnic-specific predisposing genetic factors that promote the development of specific breast tumor subtypes, and emphasize the importance of evaluating the relationship between breast cancer risk factors and breast tumor subtypes among different ethnic populations.