Thirty-three esophageal tumors were analyzed by immunohistochemistry for P53 nuclear protein accumulation, and the results were compared to p53 gene mutations by PCR-direct sequence analysis. A highly significant correlation between the presence of p53 mutations and p53 nuclear protein accumulation was found. Of 33 tumors, 23 (69.7%) that demonstrated P53 protein expression 12(36%) had p53 mutations. Of 12 tumors with p53 mutations, 9 tumors showed P53 intensive nuclear reactivity. The results reported here are consistent with the idea that p53 mutations may be an important biological event in esophageal cancer progression and P53 expression was correlated with p53 gene mutation.