Motility-related protein-1 (MRP-1)/CD9 is a trans-membrane glycoprotein closely associated with suppression of cell motility and reduced metastatic potential of some tumor cells. We currently report that, according to the RT-PCR method for MRP-1/CD9 gene expression, patients with low expression of MRP-1/CD9 in non-small-cell lung cancer, especially the adenocarcinoma type, showed short overall survival. Then, to determine accurately the prognostic value of MRP-1/CD9 product levels in lung-adenocarcinoma cells, we immunohistochemically investigated its expression in 132 lung-adenocarcinoma patients undergoing potentially curative surgery. Of these patients, 44 (33%) showed reduced expression of MRP-1/CD9 in cancer cells, and an inverse association was observed between its expression and factors associated with tumor progression, such as nodal involvement (p 5 0.029) or stage (p 5 0.028). Patients with reduced expression of MRP-1/CD9 showed a significantly worse prognosis in overall survival (p 5 0.005) and disease-free survival (DFS; p F 0.0001) than those with stronger expression; and even among patients with stage-I disease, similar results were obtained (overall survival, p 5 0.038; DFS, p 5 0.012). In a multivariate analysis, immunohistochemical MRP-1/CD9expression level was an independent prognostic factor for DFS (p 5 0.021), but not for overall survival (p 5 0.572). Thus, immunohistochemical MRP-1/CD9-expression level solely in lung-adenocarcinoma cells within the tumor tissue appears to be a prognostic factor for DFS, and may be useful for detecting a high-risk sub-group of recurrence during the post-operative clinical course of the disease. Int.