Among premalignant oral lesions, MGMT methylation frequency in tissue samples was the highest for leukoplakia with dysplasia (73%, P = 0.0002) followed by leukoplakia without dysplasia (73%, P = 0.0015), SMF (46%, P = 0.0437), and OLP (25%, P = 0.4386 NS). This evidence concerns the gene MGMT and leukoplakia.