The significance of the p73 gene, a homologue of the p53 gene, in esophageal cancers is not fully understood. In order to clarify the role of p73 expression in esophageal cancers, p73 expression was immunohistochemically investigated in 106 surgically resected esophageal cancers and the results were compared with various clinicopathological factors. In normal esophageal epithelium, the expression of p73 was observed only in the nuclei of basal cells. In esophageal cancers, p73 immunoreactivity was observed in all intraepithelial lesions except one cancer, and was reduced with cancer invasion, to 78% and 64% at superficial invasion and deep invasion sites, respectively. However, p73 expression was not correlated with any other clinicopathological factor. The expressions of p53 and p21 were also investigated in esophageal cancer. To evaluate the status of the p53 gene mutation immunohistochemically, two monoclonal antibodies (DO7 and PAb240) were used. There seemed to be an inverse correlation between p73 expression and p53 mutation. Moreover, the expression of p21 was highly correlated with p73 expression irrespective of the p53 mutation status. In human esophageal cancers, p73 expression decreased with increasing degree of tumor invasion, and its decreased expression in local advanced tumor caused down-regulation of p21 expression, which might reflect tumor progression.