The correlation between the clinical outcome in patients with esophageal squamous cell carcinoma and coamplification of the proto-oncogenes int-2 and hst-1, which are partially homologous to angiogenesis-inducing fibroblast growth factor, was analyzed retrospectively. Coamplification of these genes was examined by slot-blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded blocks of tissues. These tissues were obtained from 107 patients with esophageal squamous cell carcinoma who had undergone radical surgery. Int-2/hst-1 coamplification greater than 3-fold was observed in the primary tumors of 30 of 107 cases (28%), and in the metastatic lymph nodes of 12 of 40 cases (30%). The cumulative survival rate of patients with int-2/hst-1 coamplification in the primary tumors was significantly lower than that of the patients without coamplification (P less than 0.001), and there were no significant differences between the clinicopathological backgrounds of the 2 groups. Int-2/hst-1 coamplification was also significantly correlated with a high incidence of eventual metastasis in distant organs in these patients. These results suggest that int-2/hst-1 coamplification is a new biological indicator of prognosis and distant organ metastasis in patients with esophageal squamous cell carcinoma.