7655 Background: The role of erythropoietin (EPO) and its receptor (EPO-R) in tumor biology is under active investigation. This study was designed to evaluate the prognostic impact of EPO and EPO-R expression in stage I non-small cell lung cancer (NSCLC) patients. Methods: EPO and EPO-R expression in 158 tumor samples from resected stage I NSCLC was evaluated using immunohistochemistry and tissue-array technology. Disease specific survival time was calculated from the date of surgery to death from cancer-related causes. Results: EPOR and EPO were highly expressed in 20.9% and 35.4% of the tumors respectively. High EPO-R compared to negative or low level of expression was associated with a poor 5-year disease specific survival (60.6% versus 80.8%, logrank test: p=0.01). High EPO compared to negative and low level of expression was associated with a trend toward a poor 5-year disease specific survival (69.6% versus 80.4%, logrank test: p=0.13). High level of EPO-R and EPO coexpression compared to other groups of patients was associated with a poor 5- year disease specific survival (50.0% versus 80.0% of survival at the end of follow-up, logrank test: p=0.005). In multivariate analysis for disease specific survival, high level of EPO-R and EPO coexpression was an independent prognostic factor for disease specific survival (HR 2.214, 95% CI: 1.012–4.848, p=0.046). Conclusions: These results establish for the first time the pejorative prognostic value of EPO and EPO-R expression in early stage resected NSCLC and suggest a potential paracrine and/or autocrine role of endogenous EPO in NSCLC aggressiveness. No significant financial relationships to disclose.