The expression of the cell cycle regulatory protein p21waf1/cip1 was analyzed immunohistochemically in tissue from the tumor and adjacent non-tumor epithelia of 54 patients with tongue cancer in order to determine the proportion of tongue carcinomas with altered p21waf1/cip1 expression, establish whether this alteration is an early event in tongue carcinogenesis and to investigate whether p21waf1/cip1 expression has predictive prognostic value in these tumors. The percentage of p21waf1/cip1-positive neoplastic cells was calculated. Adjacent non-tumor epithelium was classified as normal, hyperplastic or dysplastic, and the p21waf1/cip1 expression was only considered normal in suprabasal layers. P21waf1/cip1 expression was negative in 57.4% (31/54) of the tumors and was aberrant in the non-tumor adjacent tissue of all patients studied. Neither the absence nor the degree of p21waf1/cip1 expression influenced the survival of patients in the present series. P21waf1/cip1 system alteration may be an early and frequent event in tongue carcinogenesis.