Nectin-like molecule-5 (Necl-5) is an immunoglobulin (Ig)-like molecule that is up-regulated in many types of cancer cells. It was shown experimentally that Necl-5 enhances cell migration, proliferation, and metastasis, but its clinical significance has not been documented. The aim of this study was to observe the expression of Necl-5 in surgically resected primary lung adenocarcinomas and to investigate its clinical significance. A total of 63 surgically resected primary pulmonary adenocarcinoma tissues were investigated by immunohistochemistry for the expression of Necl-5. The relationship between expression of Necl-5 and clinicopathological features was analyzed, and the influence of Necl-5 expression on outcomes in these patients was assessed. A strong expression of Necl-5 by cancer cells was observed in 43 of the 63 tumors. The overexpression of Necl-5 by cancer cells was significantly associated with lymph node metastasis (P = 0.0398), TNM staging (P = 0.0367), and the bronchioloalveolar carcinoma ratio of tumors (P = 0.0423). Furthermore, the disease-free survival rate in patients with positive Necl-5 overexpression was significantly lower than that in patients with negative Necl-5 overexpression (P = 0.0004). Multivariate survival analysis revealed Necl-5 expression to be an independent risk factor for an unfavorable outcome (P = 0.0294). Additionally, an analysis including only the stage I cases revealed that the disease-free survival rate of the Necl-5-positive group was significantly lower than that of the Necl-5-negative group (P = 0.0192). These results indicate that Necl-5 plays a role in mediating tumor cell invasion and that the overexpression of Necl-5 in cancer cells has clinical significance for prognostic evaluation of patients with primary pulmonary adenocarcinoma.