The global increase in incidence and mortality, as well as the poor prognosis of oral squamous cell carcinoma (OSCC), has intensified efforts in the field of prevention and early detection of this disfiguring disease. Prevalence of OSCC is common in areas with high consumption of tobacco products and alcohol. Understanding the carcinogenicity of this cancer, using innovative techniques in genomic and proteomic analysis, is the main focus of current research in OSCC, and the hunt for potential molecular biomarkers is accelerating. Although recent advances in preventive, diagnostic and therapeutic techniques related to OSCC have yielded novel molecular targets, partially uncovered signal pathway dominance and advanced early neoplasia detection, the number of deaths attributed to this disease exceeds that reported for cervical cancer, malignant melanoma and Hodgkin's disease. Application of advanced molecular biology techniques for classification, profiling of tumour tissues and/or identification of potential markers of OSCCs is on the rise. This review aims at outlining the available knowledge on epidemiology, aetiology, molecular biology, and genomics and proteomics in relation to OSCCs.