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S100A2, a calcium-binding protein, recently became of major interest because of its differential expression during transformation and metastasis in various tumors. The purpose of this study was to investigate the prognostic significance of S100A2 expression in the early-stage non small lung cancer (NSCLC). Immunohistochemical analysis to determine the percentage of cells staining positive for S100A2 was performed on 11 NSCLC tissue microarray slides containing samples from 113 patients with pathologic stage I NSCLC who had undergone curative surgery. S100A2 was expressed in samples from 79 patients (69.9%). Kaplan-Meier analysis showed that patients whose tumors had positive S100A2 expression had a significantly lower overall survival and disease-specific survival rate at 5 years after surgery than did patients with negative S100A2 expression (p< 0.001 andp< 0.001, respectively). Age at diagnosis, histologic type of cancer, degree of differentiation and smoking history did not have a statistically significant effect on survival. Multivariate analysis confirmed that S100A2 expression is a better predictor for disease-specific survival than were other clinical and histologic variables tested. Our results suggested that the expression of the S100A2 protein in stage I NSCLC indicates poor prognosis and may be used to identify patients with early-stage NSCLC who might benefit from adjuvant treatment.