Regional metastasis is an important prognostic factor for esophageal squamous cell carcinoma (ESCC). A reduced expression of cell adhesion molecules has been reported to be associated with tumor metastasis. However, the clinical significance of such adhesion molecules in metastatic lymph nodes remains unclear. The expression of adhesion molecules (E-cadherin, beta-catenin, CD44, CD44-v6 and Integrin beta 1) was studied in 71 primary tumors and their corresponding nodal metastases using immunohistochemical analyses. Regarding the clinicopathological features, a reduction in the expression of adhesion molecules in primary tumors was found to be significantly associated with the depth of invasion, lymph node metastasis, lymph and blood vessel permeations (p < 0.05). There was a significantly positive correlation between E-cadherin and beta-catenin (R = 0.55, p < 0.001), CD44 and CD44-v6 (R = 0.65, p < 0.001) in the primary tumor. In lymph node metastasis, there was significantly less staining for E-cadherin (p < 0.01), CD44 (p < 0.01), CD44-v6 (p < 0.05) and Integrin beta 1 (p < 0.01) in lymph node metastasis than in the primary tumor, and a significantly positive correlation between E-cadherin and beta-catenin (R = 0.55, p < 0.001). Regarding the number of lymph node metastases, a significant difference was found, and a reduced expression of E-cadherin, beta-catenin and CD44-v6 in the metastatic lymph nodes correlated with an increased number of lymph node metastases (p < 0.01). These findings are consistent with the idea that adhesion molecules have their own alterations, and a reduced expression of adhesion molecules in the metastatic lymph nodes correlated with an increased number of lymph node metastases.