Normal human palatal epithelium is an orthokeratinizing tissue with a well-developed stratum corneum. Several cytological and histological studies showed that when the palate covered by a denture fully or partially, keratinization of the mucosa changes. The results of some studies suggested that keratinization changes from orthokeratosis to parakeratosis, and there is a reduction in the thickness of stratum corneum. Whereas the results of some other studies showed increased orthokeratinization. This study was planned to determine changes in keratinization of palatal mucosa in denture wearers compared with normal palatal mucosa. Keratinization of palatal mucosa was examined by mainly exfoliative cytology in three groups. Group-1 consisted of 51 patients wearing metal-based removable partial denture; group-2 consisted of 50 patients wearing acrylic-based complete denture and group-3 including 57 healthy volunteers who have not been wearing denture served as the controls. In each group, the results of exfoliative cytology were supported by histological examinations. Statistical results showed that either acrylic-based complete or cobalt-chromium-based removable partial dentures seem to reduce the quantity and/or quality of the keratin layer. The mean values of keratinization and the thickness of stratum corneum were significantly lower in the complete denture group than in the partial denture group. Furthermore the reliability of exfoliative cytology was confirmed by the guidance of histological examination.