Refinements in oral exfoliative cytology may make it a suitable screening technique for the early diagnosis of oral cancer. In this study DNA range profiles were combined with keratin expression in an attempt to improve the diagnostic accuracy of oral exfoliative cytology. Smears were taken from 33 biopsy-proven oral cancers and the contralateral normal site. For DNA range profiles the smears underwent Feulgen hydrolysis, with DNA distribution being assessed using the Vickers M85 microdensitometer. For keratin expression a panel of antikeratin antibodies were applied. The smears for keratin expression were then graded on a three-point scale. Abnormal DNA range profiles were observed in 23 of 33 smears taken from oral cancers and in two smears from normal oral mucosa (sensitivity 70%, specificity 90%, positive predictive value 90%). The simple epithelial keratins 8 and 19 were identified in the majority of oral cancer smears. The sensitivity of keratin 19 was greater (90%). However, keratin 8 was the most useful keratin marker associated with malignancy (sensitivity 62%, specificity 100%, positive predictive value 100%). The combination of simple keratin expression and DNA content improved the cancer detection rate beyond that obtainable with DNA range profile alone.