Molecular genetic analysis indicates that the BRCA2 gene plays an important role in familial male breast cancer. To determine a possible involvement of this tumor suppressor gene in sporadic male breast cancer, we examined 30 sporadic male breast carcinomas for loss of heterozygosity (LOH) at two loci on chromosome 13q12-13, a region that spans the BRCA2 locus. Sixteen of 24 (67%) informative cases showed LOH in at least one marker on chromosome 13q12-13. The affected cases included both invasive ductal carcinomas and other types of invasive breast carcinoma and were detected preferentially in patients who were 50 years or older, in patients with lymph node metastasis, and in progesterone receptor-negative cases. We report, for the first time, a high frequency of LOH at chromosome 13q12-13 in sporadic male breast cancer and its association with factors indicating a poor prognosis for this tumor (e.g., lymph node metastasis and negative progesterone receptor status). These findings suggest an important role for BRCA2 in the development and progression of sporadic male breast cancer.