It has been suggested that an alteration in the adenomatous polyposis coli (APC) gene, which is a tumor suppressor gene, is one of the earlier events in carcinogenesis of some adenocarcinomas. We undertook this study to determine the prevalence of loss of heterozygosity (LOH) of the APC gene in several kinds of cutaneous tumors. Fifty-seven unrelated Japanese patients were examined for analysis of the APC gene. The 57 cases consisted of extramammary Paget's disease, squamous cell carcinoma (SCC), eccrine poroma and porocarcinoma, metastatic tumor of rectal adenocarcinoma and malignant melanoma. DNA was extracted from the tumor and normal portions dissected from the formalin-fixed paraffin-embedding sections and amplified with the use of the PCR. The amplified DNA was examined for LOH in the APC gene. Seven samples of 32 heterozygous persons of APC gene (three out of seven eccrine poromas, two eccrine porocarcinomas and two metastatic tumors of rectal adenocarcinoma) showed for LOH in the APC gene. None of the heterozygous samples from the extramammary Paget's disease (11), SCC (five) and melanoma (five) showed LOH. These results suggest that tumor or tumor suppressor genes, other than the APC gene, may be responsible for extramammary Paget's disease and SCC and that LOH involving APC may have some relevance to the formation and progression of eccrine tumors as in rectal tumors.