The 185delAG and 5382insC founder mutations account for the majority of mutations identified in BRCA1 in Ashkenazi Jewish breast and breast-ovarian cancer families. Few non-founder BRCA1 mutations have been identified to date in these families. We initially screened a panel of 245 Ashkenazi Jewish breast-ovarian cancer families with an affected proband and at least one other case of breast or ovarian cancer for founder mutations in BRCA1 and BRCA2. Founder mutations were identified in 85 families (185delAG in 44 families, 5382insC in 16 families, and the BRCA2 6174delT in 25 families). The 160 negative families were then screened for the entire BRCA1 gene by a combination of DGGE and PTT. We identified one novel frameshift mutation in BRCA1 in exon 14 (4572del22) that truncated the protein at codon 1485. The family contained three cases of early-onset ovarian cancer (41 years, 43 years, and 52 years) and one case of breast cancer (at age 54 years subsequent to an ovarian cancer). In addition, three missense variants of unknown significance (exon 11 C3832T (P1238L), exon 15 G4654T (S1512I), and exon 15 G4755A (D1546N)) were found in single families. These missense variants have been previously identified in other families [BIC Database] and are considered to be "unclassified variants, favoring polymorphism." Non-founder BRCA1 mutations are rare in Ashkenazi Jewish breast/ovarian cancer families.