Recent studies have suggested that bone mineral density (BMD) is related to risk of breast cancer in elderly women. This study investigated whether the level of breast cancer risk associated with BMD in women with a positive family history of breast cancer is different from that in women without a family history of breast cancer. Radial and calcaneus BMD were measured at baseline (1986-1988) in 7,250 elderly white women enrolled in the Study of Osteoporotic Fractures, and initial breast cancer status was ascertained at year 1 of follow-up. After a mean of 3.2 years of additional follow-up, 104 incident breast cancer cases, 20 of which appeared in women with a family history of breast cancer, were identified and confirmed by medical record review. Modification of the BMD effect by family history status was assessed by inclusion of interaction terms in proportional hazards regression models. Among women without a family history of breast cancer, those with a proximal radius BMD in the highest tertile were at a 1.48-fold increased risk compared with women in the lowest tertile; among women with a positive family history of breast cancer, those with highest tertile BMD were at a 3.41-fold increased risk compared with women in the lowest tertile. These results suggest that the association between BMD and breast cancer may be different in subgroups of women defined by family history.