PURPOSE: To test whether female subjects in families with cleft lip and/or palate (CL/P) have an increased risk of breast cancer. METHODS: By using the Danish Facial Cleft Registry, we identified female subjects with CL/P, mothers of children with CL/P, and sisters to CL/P cases for the Danish birth cohorts 1911-1975. These subjects were compared with a 5% random sample of these cohorts regarding the incidence and age of onset for breast cancer registered in the Danish Hospital Discharge Register 1977-2005. RESULTS: Examining 48,404 person-years for 1809 female CL/P cases (49 breast cancer cases) and 212,795 person-years for 7935 female relatives (188 breast cancer cases), we found no increased breast cancer risk for either CL/P cases (hazard ratio [HR], 1.23; 95% confidence interval (CI), 0.92-1.63), mothers of children with CL/P (HR, 0.93; 95% CI, 0.80-1.08), or sisters of CL/P cases (HR, 0.94; 95% CI, 0.55-1.60), nor was there any significant differences in age of onset. CONCLUSION: Both epidemiological and genetic studies have suggested common etiological factors for breast cancer and CL/P. However, in this population-based study we were not able to confirm a general increase in the risk of breast cancer among female subjects in families with CL/P.