Connexin 43(Cx43) and E-cadherin are concurrently expressed in many tumors and were ever classified as tumor suppressors in primary tumors (PT), whereas recent studies showed that these two proteins played specific roles in tumor metastasis. The aim of our study is to determine the expression of Cx43 and E-cadherin in primary gastric tumors (PTs) and matched metastatic lymph nodes (MLNs) and to explore the clinical and pathological implications of expression of these proteins. Immunohistochemical assay was conducted to detect the expression of Cx43 and E-cadherin in PTs and MLNs, and the clinical and pathological implications were analyzed by statistical methods. In PTs, the expression of Cx43 and E-cadherin was significantly reduced, compared to adjacent normal tissues (P < 0.01). The expression of Cx43 and E-cadherin was significantly increased in MLNs compared with PTs (P < 0.01 and P < 0.01, for Cx43 and E-cadherin, respectively), and some Cx43 and E-cadherin-negative PTs developed Cx43 and E-cadherin-positive MLNs. Furthermore, reduced expression of both Cx43 and E-cadherin significantly correlated with poor differentiation, advanced TNM stage, and lymph note metastasis of gastric cancers. Cx43 and E-cadherin expression significantly correlated with each other. We concluded that concurrent reduction in Cx43 and E-cadherin may contribute to the occurrence of gastric cancer. However, concurrent increased expression of Cx43 and E-cadherin may contribute to the efficient metastasis of gastric cancer to the lymph nodes.