Background: The purpose of this study was to investigate differences in epidemiology, types of presentation, time between diagnosis and treatment, tumor characteristics, and survival in patients 45 years or younger with non-small cell lung cancer. Methods: A nested case-control study was conducted during 7 years using a prospective database of patients with non-small cell lung cancer. Younger patients (<45 years of age) were matched 1:2 with older patients for stage, sex, performance status, and type of resection. Results: There were 762 patients (254 were <45 years old, 508 controls were older). The median time from initial symptom to thoracic surgical consultation was significantly longer for those younger than 45 years (6.5 versus 2.8 weeks; p < 0.001). Younger patients were more likely to be symptomatic at the time of diagnosis (89% versus 68%; p < 0.001) and less likely to be smokers (45% versus 78%; p < 0.001). Kaplan-Meier analysis showed the time between diagnosis and treatment, symptoms, maximum standardized uptake value on positron emission tomography, and smoking status impacted survival. Only symptoms and smoking status impacted survival on Cox proportional hazards survival analysis among completely resected patients; 5-year survival was lower in the younger group compared with the older group (51% versus 62%; p = 0.037). Conclusions: Despite similar stages and tumor characteristics patients younger than 45 years of age with non-small cell lung cancer have a significantly worse prognosis than older patients. Although they are more likely to be symptomatic, younger patients have a greater delay in seeking thoracic surgical care. These data should be considered in the treatment strategy offered to younger patients with non-small cell lung cancer. © 2008 The Society of Thoracic Surgeons.