Accurate diagnosis of oral hairy leukoplakia (OHL) is important because it may be an early indicator of undiagnosed HIV infection; moreover, it may be a prognostic indicator. Our purpose was to investigate the histopathologic features of subclinical OHL and to evaluate and support the rationale of detecting subclinical OHL with cytopathology. The Epstein-Barr virus (EBV) was detected by immunohistochemistry and in situ hybridization in 4 cases of macroscopically normal lateral borders of tongue mucosa from 8 AIDS necropsies and in none of 8 controls. The histopathologic features were specific when based on nuclear changes: Cowdry type A inclusion, ground glass, and nuclear beading. Smears were obtained from 50 patients with AIDS, without OHL, from the scraping of lateral borders of the tongue. Numerous clusters of the cells were associated with Candida organisms (30% of cases). Nuclear changes were observed in 12 patients (24%) on both sides of the tongue. We describe the histopathologic features of subclinical OHL, and our observations suggest that cytopathology can detect OHL in the subclinical phase.