Male breast cancer is a relatively rare disease that represents about 1% of all male malignancies. Its genetic basis has received little attention. Allelic imbalance, reflected by change in microsatellite repeat number (MSI) or loss of heterozygosity (LOH), is thought to play an important role in carcinogenesis. In this study we have examined DNA extracted from paraffin tissue from 15 patients treated for male breast cancer, for evidence of such abnormalities, at 20 different loci across the genome. Polymerase chain reaction amplified products of normal and tumor DNA pairs were compared by electrophoresis on Spreadex gels. MSI was detected in 5 patients; at a single site in 2 cases and at 3, 7 and 9 sites in another 3 cases. LOH was seen in 8 cases (53%); at more than one site in 4 of these. Two patients had allelic variation at 56 and 62% of assessable sites. The most unstable loci were D2S441 (33%) and D13S325 (27%). These observations indicate that replication errors and allelic loss characterise male breast cancer tissue in much the same way as they do in women. More studies will be needed to establish whether these are random lesions or whether there are specifically affected sites that occur in both male and female breast cancer.