Some investigators have suggested that mutations of the p53 gene may be molecular markers for poor prognosis of cancer patients, although others have reported conflicting results. We examined esophageal cancers from 138 patients to investigate whether mutational status of p53 could be correlated either with prognosis or with response to chemotherapy or radiation. We detected p53 mutations in the tumors of 78 (56.5%) patients. Kaplan-Meier analysis showed that these 78 patients tended to have shorter survival times and greater resistance to either form of therapy than patients whose tumors carried two wild-type p53 alleles. The difference became more evident when we focused on mutations in zinc-binding domains of p53 (L2 and L3); the prognosis was significantly poorer among the 29 patients with tumors in this category than among patients whose tumors had no p53 mutations, or p53 mutations outside L2 or L3 (P=0.0060). Moreover, those tumors as a group were more resistant to chemotherapy or radiation than the others (P=0.0105). Our results underscore the importance of the zinc-binding domains of p53 with respect to clinical prognosis for patients with esophageal carcinomas.