The association between mammographic breast density and breast cancer risk may be the result of genetic and/or environmental factors that determine breast density. We reasoned that if the genetic factors that underlie breast density increase breast cancer risk, then breast density should be associated with family history of breast cancer. Therefore, we determined the association between mammographic density and family history of breast cancer among women in the San Francisco Mammography Registry. Mammographic density was classified using the four BI-RADS criteria: 1 = almost entirely fatty, 2 = scattered fibroglandular tissue, 3 = heterogeneously dense, and 4 = extremely dense. We adjusted for age, body mass index, hormone replacement therapy use, menopause status, and personal history of breast cancer. Compared with women with BI-RADS 1 readings, women with higher breast density were more likely to have first-degree relatives with breast cancer (BI-RADS 2, odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.96 to 1.89; BI-RADS 3, OR = 1.70, 95% CI = 1.19 to 2.40; BI-RADS 4, OR = 1.70, 95% CI = 1.05 to 2.71). Thus, the genetic factors that determine breast density may determine breast cancer risk.