Defective mismatch repair has been detected in human colorectal and endometrial carcinomas which exhibit microsatellite instability (MIN). The purpose of this study was to search for MIN in melanoma. Paraffin-embedded neoplastic and non-neoplastic control cells were obtained from 20 untreated individuals with cutaneous malignant melanoma. Breslow thickness ranged from 0.2-7.4 mm (mean 1.4). Cells were carefully scraped from glass slides so that tumor and control DNA could be isolated and then amplified by polymerase chain reaction (PCR) at seven separate microsatellites localized to specific chromosome regions: 1p22 (D1S187), 5q11.2-13.3 (D5S107), 6q21-23.3 (D6S357), 9p21 (IFNA), 11p15.2 (D11S861), 17p13.1 (D17S786), and 18q11 (D18S34). Heterozygosity indices were > or = 0.70. Loci from these chromosome regions were chosen because of cytogenetic abnormalities reported in melanoma (1p, 6q, 9p), location of common oncogenes (11p-HRAS, 17p-TP53), or use in other MIN studies (5q, 18q). Five individuals (25%) demonstrated MIN. There was no correlation with tissue thickness. One individual demonstrated MIN at two loci and one individual demonstrated loss of heterozygosity. The results indicate that MIN occurs in melanoma, albeit less frequently than reported in carcinomas.