New onco-suppressor gene p130 is one of the Rb family forms and is reported to undergo allelic loss in hepatocellular, prostate, and breast carcinomas; however, no report of p130 has been made in oral tumors. The present study dealt with the expression of p130 and Rb proteins by immunohistochemical staining in oral squamous cell carcinomas (n = 110) and oral mucosa. The site of the carcinomas included tongue (n = 48), gingiva (n = 32), oral floor of the mouth (n = 15), oropharynx (n = 6), buccal mucosa (n = 5), and others (n = 4). Histologically there were 65 well-differentiated carcinomas, 33 moderately differentiated carcinomas, and 12 poorly differentiated ones. Positive staining for p130 and Rb was localized to suprabasal cell layers of the normal oral epithelium. In the oral squamous cell carcinoma, positive staining for p130 and Rb was observed in well-differentiated carcinomas (p130, 66.2%; Rb, 78.5%), more than in poorly differentiated ones (p130, 16.7%; Rb, 50.0%). In immunoelectron microscopic features, p130 protein was localized in the nucleus and mitochondria. The expression of p130 was related to the degree of tumor differentiation as that of Rb. It is suggested that p130 gene may be associated with the development of a wide variety of human malignancies rather than the progression.