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Oral Cancer (OC) is a subset of head and neck cancer (HNC) with an annual worldwide incidence of 275,000 cases. OC remains a significant burden worldwide in terms of diagnosis, treatment and prognosis. Despite desirable outcomes in early diagnosed OCs and treatment advances most OCs are detected in advanced stages. The 5-year survival rate of early-stage disease is ∼80% and that of late-stage disease is only ∼20%. Recurrence and chemoresistance from a treatment point of view and pain and disfiguration are important factors contributing to the high morbidity and mortality of OC. Furthermore the process of oral carcinogenesis is complex and not yet fully understood. Consequently numerous potential biomarkers have been hypothesised though controversial results across the board hamper their clinical implementation. Of greatest advantage would be biomarkers signalling early events preceeding OC. Biomarker targets predominately involve deregulated molecular events that participate in cell signalling, growth, survival, motility, angiogenesis and cell cycle control but can also use changes in metabolic genes to discriminate healthy form disease state. Promising potential biomarkers include the growth signalling oncogenes, Epidermal Growth Factor Receptor and Cyclin D1, the anti-growth signalling components p53 and p21, apoptotic effectors such as Bcl-2 and also components involved in immortalisation, angiogenesis, invasion and metastasis processes. Translation of these potential biomakers to the patients is closer than ever though few issues remain to be resolved. Firstly large clinical trials are needed to validate their clinical applicability but also standardised methods of collection, storage and processing methods are needed to minimise variability.