The messenger RNA level of several MAGE genes, some of which have been proven to encode tumor rejection antigens recognized by cytotoxic T lymphocytes, were examined in 41 benign and malignant lesions of the head and neck region. By a reverse transcription-polymerase chain reaction assay and Southern blot hybridization, MAGE-1, -2, -3, -4, and -6 genes were expressed in 25%, 41.7%, 33.3%, 8.3% and 33.3% of 12 non-squamous cell carcinomas, respectively. These tumors consisted of 6 papillary adenocarcinomas, 3 adenoid cystic carcinomas, 2 adenocarcinomas, and 1 mucoepidermoid tumor. Of 7 non-Hodgkin's lymphomas, one case from the oropharynx and 2 from the nasopharynx expressed for the MAGE-1 and MAGE-2 genes, respectively. In contrast, none of 12 benign tumors expressed any of these MAGE genes. Interestingly, of 10 other lesions including hyperplasia, keratosis, and ulcer, one histologically diagnosed as dysplasia expressed the MAGE-2, -3, -4, and -6 genes. These results suggest that the MAGE genes may be expressed in malignant tumors and precancerous lesions but not in benign tumors. In addition, non-squamous cell carcinomas may be suitable targets for specific immunotherapy against MAGE gene products.