The purpose of this study was to investigate the molecular biological characteristics of malignant mucosal melanoma (MMM) and adenoid cystic carcinoma (ACC) of the head and neck. We analyzed the common genetic abnormalities that may help to identify the loci in the genes involved in the development of MMM and ACC of the head and neck by PCR-LOH on chromosomes 1p, 6q, 9p, 10q, 11q, 12q, 17p, and 19q. LOH was observed in 6 of 12 cases of MMM and in 12 of 15 cases of ACC informative for at least one of the loci analyzed. One distinct deleted region was identified at chromosome 9p21. In addition, to identify a possible involvement of p16/CDKN2 PCR-SSCP and auto-DNA sequence analysis were also performed to detect any mutation of the p16/CDKN2. Particularly, 2 missense mutations were detected in codon 225 and 226, both in MMM and ACC. There were mutational hot spots in the p16/CDKN2 gene. These results suggested that mutation of the p16/CDKN2 gene was a common factor in the development of human MMMs and ACCs, while this gene may be correlated with development and/or progression of a subtype and play a role in the oncogenesis of these cancers.