A subgroup of pleomorphic adenomas of the salivary glands is characterized by translocations involving chromosome 12, with consistent breakpoints at 12q13-15. Two proto-oncogenes, INT1 and GLI, have been assigned to this region of chromosome 12. We studied the possible involvement of these genes in pleomorphic adenomas with different karyotypic abnormalities, including cases with involvement of 12q13-15. Using detailed restriction fragment analysis of tumor DNAs from 25 cases, we found no evidence of rearrangement or amplification of INT1 or GLI. Because we previously found an adenoma with a del(12)(q13q15), we also analyzed normal and tumor DNAs from the 25 tumors separately to identify possible allelic losses at the GLI locus. Thirteen of the 25 tumors were informative, and none of these showed evidence of allelic losses. Collectively, these findings indicate that neither the INT1 nor the GLI gene appears to be the primary target gene for the translocations and deletions involving the 12q13-15 region in pleomorphic adenomas.