Methylation of specific lysine residues in histone tails has been proposed to function as a stable epigenetic marker that directs biological functions altering chromatin structure. Recent findings have implicated alteration in heterochromatin formation as a contributing factor in cancer development. In order to verify whether changes in the overall level of H3K4 histone methylation could be involved in oral squamous carcinoma, the levels of H3K4me1, me2 and me3 were measured in oral squamous carcinoma, leukoplakias and normal tissues. The levels of H3K4me2 and me3 were significantly different in oral squamous cell carcinoma in comparison with normal tissue: the level of H3K4me2 was increased while that of H3K4me3 decreased. No significant differences could be found between the two types of tissues in the level of H3K4me1. A similar trend was found in the leukoplakias that appeared more like the pathological than normal tissue. These results support the idea that alteration of chromatin structure could contribute to oncogenic potential.