It has been suggested that inactivation of the cadherin-mediated cell-cell adhesion system plays a role in the initial steps of cancer invasion and metastasis. Expression of E-cadherin and its intracytoplasmic binding molecules, α-catenin, β-catenin and plakoglobin was examined immunohistochemically in 96 esophageal squamous cell carcinomas to investigate the association between their expression and the prognosis for patients with esophageal cancer. Reduced E-cadherin, α-catenin, β-catenin and plakoglobin expression was observed in 44, 72, 73 and 88% of the tumors, respectively. Reduced E-cadherin, α-catenin, β-catenin and plakoglobin expression correlated closely with the differentiation grade of the esophageal squamous cell carcinoma (p < 0.05). Downregulation of α-catenin was associated with a poor prognosis in patients with esophageal squamous cell carcinoma (p < 0.05). This result suggests that downregulation of α-catenin, which may reflect dysfunction of the cadherin-mediated cell-cell adhesion system, is a factor indicating a poor prognosis in patients with esophageal cancer.