Background: Estrogen and growth factor pathways are potential targets for novel preventative and treatment strategies of lung adenocarcinoma. The purpose of this study is to examine the correlation among estrogen receptor (ER), aromatase expression, and other prognostic factors including epidermal growth factor receptor (EGFR) mutation in lung adenocarcinoma. Methods: We evaluated 150 resected primary lung adenocarcinoma specimens. Expression of aromatase, ERα, ERβ, progesterone receptor (PR), and HER2 was evaluated with immunostaining. Aromatase expression was scored from 0 to 3+ according to immunoreactive intensity. EGFR mutation was evaluated with SmartAmp2 method. Overall survival (OS) and recurrence free survival (RFS) was calculated by Kaplan-Meier method, and differences in survival were determined by log-rank test. Cox proportional hazards model was used to evaluate independent prognostic factors. Results: Expression of aromatase, ERα, ERβ, PR, and HER2 were detected in 79.3%, 1.3%, 88.0%, 2.7%, 39.3% of all patients, respectively. In all patients, high aromatase expression (2+, 3+) was an independent predictor of poor OS (Hazard Ratio [HR]=2.3; 95% confidential interval [CI], 1.2-4.4; P= .017), while no prognostic significance was seen in RFS. ERβ was not an independent predictor of OS and RFS. In patients with wild-type EGFR, high aromatase expression was an independent predictor of poor OS (HR=2.6; 95%CI, 1.2-5.9; P= .019) and RFS (HR=2.5; 95%CI, 1.2-5.4; P= .020). Positive ERβ was also an independent predictor of poor RFS (HR=4.0; 95%CI, 1.2-13.2; P= .022). Furthermore, high aromatase expression was a significant predictor of poor survival only in women (OS, P= .010; RFS, P= .007), while positive ERβ was a significant predictor of poor survival only in men (OS, P= .073; RFS, P= .051). No prognostic significance was seen in patients with EGFR mutations. Conclusions: Aromatase and ERβ expression were independent negative prognostic factors in EGFR wild-type adenocarcinoma. We further showed that in patients with wild-type EGFR, high aromatase expression was a significant predictor of poor survival only in women, while ERβ expression was a significant predictor of poor survival only in men.