Multiple genetic and epigenetic changes in critical regulatory genes have a role in the development of oral cancer. When genes are silenced by abnormally high levels of promoter hypermethylation, they have the potential to serve as biomarkers for early diagnosis, tumor molecular subtyping, prognosis and treatment monitoring. Different liquid biopsies have been found to have abnormal DNA methylation, which may be a viable alternative to solid biopsies. Noninvasive mouth cancer screening and early diagnosis could benefit from saliva testing for methylation genes. Gene promoter hypermethylation in saliva is examined here.