As the therapeutic options for malignant lesions expand, early accurate diagnosis of premalignancy is becoming increasingly important in the concept of cancer prevention. Because it has been hypothesized that abnormal cell proliferation is related to subsequent malignant transformation, many proliferation markers such as proliferating cell nuclear antigen have been studied in a variety of malignant tumors. In oral surface epithelium, proliferating cell nuclear antigen activity is restricted to basal layers of normal squamous mucosa. In this preliminary study, 169 formalin-fixed, paraffin-embedded oral epithelial lesions, including 28 carcinomas in situ, 82 epithelial dysplasias, 21 epithelial atypia, and 38 typical epithelial hyperplasias, were studied with a monoclonal antibody, PC10, to determine whether proliferating cell nuclear antigen suprabasal expression correlated with premalignancy. The findings revealed that with progression of lesions toward malignancy, there was a significant predilection for basal/suprabasal staining pattern for proliferating cell nuclear antigen as compared with the strictly basal staining pattern seen in normal and benign epithelial conditions. One unexpected staining pattern, suprabasal positive stain only, was also noted mostly in reactive hyperplasia and dysplasia. The data suggested that a positive basal/suprabasal staining pattern for proliferating cell nuclear antigen is indicative of premalignancy in oral epithelial lesions.