Background. Estrogen receptor (ER) and progesterone receptor (PR) play important roles in breast cancer. Similarly, there have been several reports of ER and PR expression in lung cancers, but the results have not been consistent. The aim of this study was to investigate the association between hormone receptor expression and clinicopathologic factors and epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Methods. We evaluated 316 resected NSCLC specimens for ER-alpha, PR, human epidermal growth factor receptor 2, and aromatase (n = 272) expression using immunohistochemical methods. EGFR mutations were evaluated with polymerase chain reaction (PCR). Results. ER-alpha and PR were detected in 36.1% and 44.9% of all patients, respectively. The expression of ER-alpha was observed mostly in cytoplasm (94.7%) and the expression of PR was observed mostly in nucleus (95.8%). Aromatase was detected in the cytoplasm of 64.0% of patients. ER-alpha expression was significantly associated with female gender (p = 0.004). The expression of PR was significantly associated with better clinicopathologic features. ER-alpha expression showed a positive correlation with PR (r = 0.275; p < 0.001) and aromatase (r = 0.244; p < 0.001) expression levels. EGFR mutation was independently associated with the female gender (p = 0.001), negative expression of PR (p < 0.001), and negative expression of aromatase (p = 0.027). Conclusions. The expression of ER-alpha and PR distinguish a subset of NSCLC that has defined clinicopathologic features. Negative expression of PR and aromatase correlate with EGFR mutation. (Ann Thorac Surg 2011;91:1562-7) (C) 2011 by The Society of Thoracic Surgeons