Investigators disagree regarding the value of exfoliative cytology in the diagnosis of oral cancer. The objective of the present study was to examine exfoliated oral epithelial cells from malignant lesions of the oral mucosa by means of Scanning electron microscope (S. E. M.) in order to determine whether SEM surface characteristics might be useful and specific to predict more accurately the nature of these lesions. Twenty cases of squamous cell carcinomas of non keratinized sites of the oral mucosa (Cheek and floor of the mouth) were selected for this study. Exfoliated cells were collected by scraping by means of modified Ayre's spatula and spread over a standard glass microscope slide for light microscope examination, while those for SEM were spread evenly on a plastic square (1 cm2) cut from a polyester sheet of Melinex "O" (Firket 1966). Altered tissue architectures and cell surface architectures were demonstrated in malignant oral lesions. Bizarre cell forms often showing an absence of close cell-cell contact relationships were seen. The observed cell surface patterns were apparently not related to the degree of keratinization when compared to normal surface patterns of corresponding areas of oral mucosa studied in a previous work. These changes appeared to some extent to be related to the clinical diagnosis and to the degree of epithelial atypia observed by the lesions. In conclusion the observations made in this study demonstrate that surface structural differences exist between exfoliated cells from malignant lesions of the oral mucosa and those from corresponding normal non keratinized sites and that the SEM might be of a diagnostic value.