Genetic alterations that lead to loss or changes in tumour-suppressor genes are known to contribute to oral carcinogenesis. Traditional molecular methods to detect such losses have relied on mutation analysis or deletion of the gene. However, epigenetic mechanisms could also contribute to silencing of tumour-suppressor genes. Methylation regions rich in CpG promoters prevent DNA transcription by changing the binding of histone complexes. The substantial contribution of methylation, specifically in oral squamous-cell carcinoma, is now being realised and investigated.