The present study evaluated 5 of the 8 main TP53 mutation hot spots in cancer by restriction site mutation analysis and compared the results with p53 protein expression in patients with cancer of the tongue. Tumor samples from 49 patients with tongue cancer were screened for TP53 mutations in exons 5 through 8 by PCR restriction site mutation analysis and for p53 protein expression by immunohistochemistry using the DO-7 antibody. Nuclear accumulation of p53 protein was seen in 22% (11/49) of the tumors, whereas none of the patients exhibited TP53 mutations in exons 5 through 8. The observed data suggest that TP53 mutations alone are not responsible for abnormal accumulation of p53 protein in tobaccochewing-mediated tongue carcinogenesis.