Rationale: The receptor for advanced glycation endproducts is a multiligand receptor that plays an important role in regulating the invasiveness and metastatic potential of cancer cells. A recently discovered novel splice variant, the endogenous secretory receptor for advanced glycation endproducts, mediates the receptor for advanced glycation endproducts-associated cell responses by functioning as a decoy receptor. Objectives: To evaluate the expression pattern of endogenous secretory receptor for advanced glycation endproducts in non-small cell lung carcinoma, and analyzing its impact on the prognosis. Methods: We performed immunohistochemical evaluation in 182 non-small cell lung carcinoma surgical specimens. The effect of an overexpressed receptor in cancer cell proliferation was also evaluated. Measurements and Main Results: The endogenous secretory receptor for advanced glycation endproducts expression in cytoplasm was reduced or absent in 137 of the 182 (75%) carcinomas in contrast to normal lung tissues. mRNA expression was also suppressed in cancer cells. Overexpression of the secretory receptor in lung cancer cell lines had an inhibitory effect on cell proliferation, suggesting the reduced receptor expression accelerated tumor growth. Among patients with low expression of the cytoplasmic secretory receptor, the overall survival rate was significantly lower than that of patients with normal expression (p=0.0003). This association was most prominent in TNM stage I patients (p=0.0001). In a multivariate analysis, endogenous secretory receptor immunoreactivity was an independent prognostic factor with a relative risk 3.1. Conclusions: The cytoplasmic endogenous secretory receptor for advanced glycation endproducts expression has the potential to be a prognostic factor for predicting the outcome of curative surgery in non-small cell lung carcinoma patients.