Our study proved that the expression of the gene coding COMT was downregulated prominently in tumor tissues compared to adjacent non-tumor tissue, and the COMT at-risk genotypes (rs4633 (C/C) and rs9606186 (G/G)) were associated with risks of oral and pharyngeal cancers and OPMD, implying that COMT may play a key role in the development of oral and pharyngeal cancers and OPMD. Here, COMT is linked to neoplasm.