Objective and methods: To characterize gender differences in lung cancer, we conducted a retrospective analysis including all patients undergoing surgery for non-small cell lung carcinoma in a single institution over a 20-year period. Results: Compared with men (n = 839), women (n = 198) were more likely to be asymptomatic (32% vs 20%, P =.006), nonsmokers (27% vs 2%, P <.001), or light smokers (31 pack-years vs 52 pack-years; P <.001), Squamous cell carcinoma predominated in men (65%), and adenocarcinoma predominated in women (54%), Preoperative bronchoscopy contributed more frequently to a histologic diagnosis in men (69% vs 49% in women, P <.001), and fewer pneumonectomies were performed in women (22% vs 32% in men, P =.01). After multivariate Cox regression analysis, women survived longer than men (hazard ratio, 0.72; 95% confidence interval, 0.56-0.92; P =.009) independently of age, presence of symptoms, smoking habits, type of operation, histologic characteristics, and stage of disease. The protective effect linked to female sex was present in early-stage carcinoma (stage I and II) and absent in more advanced-stage carcinoma (stage III and IV). Conclusions: This study emphasizes strong sex differences in presentation, management, and prognosis of patients with non-small cell lung cancer.