The diagnosis and treatment of oral premalignant lesions and squamous cell carcinoma are currently based on histopathologic features, site of involvement and stage of disease. Recent advances in techniques for detecting lesions and predicting their progression or recurrence are reviewed here. Adjuncts for detection of lesions and selection of biopsy sites include vital tissue staining (with toluidine blue) and exfoliative cytology. Advances in diagnosis and staging at the molecular level are expected to affect choice of treatment and patient outcomes. Oral health care providers should be aware of these advances in the evaluation and diagnosis of oral premalignant lesions and squamous cell carcinoma.