This article addresses several issues in the approach to diagnosis of oral cancer. The term oral cancer is clarified. Key aspects of the biologic basis of development of oral cancer and the known risk factors associated with the disease are summarized. The clinical presentation of oral cancers and precancerous lesions and their histopathologic correlates is discussed. The importance of conventional tissue biopsy as the prevailing gold standard for diagnosis is emphasized. Other current technologies available for detecting and diagnosing oral cancer and premalignant lesions are acknowledged, and their respective strengths and weaknesses are discussed.