Historically, sensitivity and specificity of oral cytology is poor. Using conventional oral cytology for the diagnosis of cancer and its precursors has not had the success that cytologists had hoped for; however, with improved methodology, oral cytology has enjoyed a resurgence of interest. This renewed interest is partly due to the introduction of a specialized brush that collects a full-thickness epithelial sample and not just superficially sloughed cells, as well as analysis of that sample with computer assistance; in addition, a variety of adjunctive techniques have been introduced to potentially enhance the diagnosis of the cytologic specimens including DNA analysis, immunocytochemistry, molecular analysis, and liquid-based preparations. An increase in sensitivity (>96%) and specificity (>90%) of the oral brush biopsy with computer-assisted diagnosis has been reported for identification of malignant and premalignant lesions. Brush cytology is valuable to prevent misdiagnosing doubtful oral lesions, i.e., those lesions without a definitive etiology, diagnosing large lesions where excision of the entire tissue is not possible or practicable, evaluating patients with recurrent malignancies, and monitoring premalignant lesions. Diagn. Cytopathol. 2012; © 2011 Wiley Periodicals, Inc.