Methylation of histones is one of the important "epigenetic" mechanisms associated with the transcriptional silencing and/or activating of tumor suppressor genes. To assess whether epigenetic phenomena could be involved in salivary gland carcinogenesis, the expression levels of four histone lysine-methyltransferases (HMT) were investigated, in both pleomorphic adenoma and the adjacent normal tissue of the parotid glands. The expression levels of three HMTs, SETB1, Eu-HMTase and SET08, were higher in tumor tissues. On the contrary, DOTL1 presented a lower expression level in the tumor tissues than in the corresponding normal tissues. These data suggest that the HMTs may be involved in the differentiation of pleomorphic adenoma, probably through chromatin structural changes, and indicates that the study of the epigenetic mechanism which modulates the variation in the methylation profile of histones may be useful to obtain information concerning those genes involved in tumor transformation in human parotid glands.