To date, over 6300 mutations in BRCA1, involving 1100 distinct sites, have been described and reported in the BIC (breast cancer information core) database. Since the first BRCA1 mutations in early-onset breast and ovarian cancer families were reported, several attempts to establish genotype-phenotype correlations for this gene have been reported. Moreover, in vitro data have suggested dominant-negative effects of putative mutant BRCA1 proteins over wild-type proteins. Genotype-phenotype correlations are not only important for predicting the clinical course of the disease and to allow tailor-made surveillance of individuals at risk, but also have implications for the elucidation of the molecular genetic mechanisms underlying BRCA1-mediated tumorigenesis and the development of gene transfer-based therapies. Here, we discuss genotype-phenotype correlations at the BRCA1 locus in mouse and man, and the functional aspects that may account for these observations.