Prevention and early detection of OSCC and its pre-invasive intra-epithelial stages is still largely based on visual examination of the mouth, although a variety of molecular techniques have been tested and are likely to represent the ultimate goal of oral cancer research. A 9-year randomized controlled trial has shown that screening via visual examination of the oral mucosa under white light is effective in reducing mortality in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as identify areas of dysplasia/early OSCC that are not visible to naked eye.