Although a clear correlation between the epigenetic-driven deregulation of gene expression and the oral cancer progression is at present not fully demonstrated, hypermethylation and consequent silencing of several tumor suppressor genes, out of a group of more than 40 genes, has been identified in OSCC [20] (Table 2); the genes found hypermethylated in OSCC cover a wide range of cellular processes, including cell cycle control (p16, p15), apoptosis (p14, DAPK, p73 and RASSF1A), Wnt signalling (APC, WIF1, RUNX3), cell-cell adhesion (E-cadherin), and DNA-repair (MGMT and hMLH1) [30–33]. This evidence concerns the gene CDKN2A and lip and oral cavity carcinoma.