Early oral cancer detection and accurate diagnosis remain the most challenging aspects of oral oncology. Heterogeneity in oral cancer (mostly squamous cell carcinoma) renders accurate classification problematic, which in turn impacts on treatment decision and patient outcome. Early oral cancer detection coupled with appropriate treatment can significantly improve patient outcome, reduce mortality and alleviate public healthcare costs. Clinical diagnosis of early potentially malignant oral lesion is one of the first challenges of dental practitioners when encountering an oral lesion. Whilst most oral lesions are clinically well characterized and easy to identify, the main problem is to be able to identify which lesions are potentially malignant.