The prevalence of disease-related BRCA1 mutations was investigated in 642 Dutch breast cancer patients not selected for family history or age at diagnosis. They were tested for germline mutations in the BRCA1 gene using an assay which detects small deletions and insertions (DSDI), as well as the two major genomic founder deletions present in the Dutch population. Data on family history and bilateral breast cancer were obtained retrospectively. Ten protein truncating mutations were detected and one in-frame deletion with an unknown relation to disease risk. Four patients carried the Dutch founder deletion of exon 22. Based on these results the estimated prevalence of breast cancer in the general population in the Netherlands attributable to BRCA1 mutations is 2.1%. Under 40 years-of-age and under 50 years-of-age this prevalence is 9.5% and 6.4%, respectively. All mutation carriers were under 50 years-of-age at diagnosis of the first breast cancer, and five did not have any relative with breast cancer. The proportions of bilateral breast cancer in the mutation carriers and noncarriers did not differ from each other. These data indicate that in the general Dutch breast cancer population the great majority of BRCA1 mutations will be found in women diagnosed under 50 years-of-age. (C) 2000 Cancer Research Campaign.