The possibility of diagnosing oral hairy leukoplakia by means of exfoliative cytology and the Papanicolaou stain was investigated. Exfoliative cytology and punch biopsy specimens were obtained from 10 lesions that demonstrated clinical features of hairy leukoplakia. All biopsy specimens demonstrated the characteristic histopathologic features of hairy leukoplakia whereas all Papanicolaou-stained cytologic smears demonstrated condensation and margination of the nuclear chromatin (nuclear beading). All biopsy specimens and cytologic smears displayed positive Epstein-Barr virus deoxyribonucleic acid in situ hybridization. We conclude that routine exfoliative cytology may be a reliable, noninvasive, and inexpensive technique for the diagnosis of hairy leukoplakia.