Growth stimulatory/inhibitory factors and their receptors are the important mediators of control of epithelial cell proliferation and differentiation. The aim of this study was to observe the distribution of epidermal growth factor receptor (EGFR) and transforming growth factor-beta1 type II receptor (TbetaRII) during carcinogenesis of oral squamous cell carcinoma (OSCC). Formalin fixed, paraffin embedded tissue from 25 oral leukoplakias (OL) and 15 OSCC was immunostained by avidin-biotin complex method. In OSCC, the carcinomatous area and the adjacent dysplastic/ hyperplastic area were examined. In OL, the hyperplasia and the epithelial dysplasia were examined. Monoclonal anti-EGFR Ab and polyclonal anti-TbetaRII Ab were applied. EGFR was mainly expressed in the basal layer and was increased with epithelial dysplasia in OL. TbetaRII was not detected in the basal cell layer and dysplastic area in OL. In contrast, the dysplastic area adjacent to OSCC showed positivity in the entire layer including the dysplastic area. In all cases of OSCC, both EGFR and TbetaRII showed positive reactions. EGFR was increased with the progression to the malignancy, and the expression pattern of TbetaR II was altered to be positive in the basal cell layer with progression to malignancy. These results suggest that the expression of EGFR appeared to be an early event and TbetaR II may be related to malignant transformation during oral carcinogenesis. The expression pattern of EGFR and TbetaR II may contribute to predict the risk of the development of carcinoma in oral premalignant lesions.