Objective: Large cell neuroendocrine carcinomas of the lung display morphologic and immunohistochemical characteristics common to neuroendocrine tumors and the morphologic features of large cell carcinomas. Surgical resection of large cell neuroendocrine carcinomas in many series has been described, with 5-year actuarial survivals ranging from 13% to 57%. Considerable debate has emerged as to whether these tumors should be classified and treated as non-small cell lung cancers or small cell lung cancers. The objective of this study was to report the outcome of surgical resection in patients with large cell neuroendocrine carcinomas. Methods: An analysis of our tumor registry was performed to identify all patients undergoing surgical resection of lung cancer between July 1, 1988, and December 31, 2002, for large cell tumors. Cases were then segregated into large cell neuroendocrine carcinomas, mixed large cell neuroendocrine carcinomas (in which at least one portion of the tumor was a large cell neuroendocrine carcinoma), or large cell carcinomas on the basis of morphology and differentiation. Follow-up was complete on all patients, with a mean follow-up of 48 months. Type of resection, mortality, and survival by stage were analyzed. Kaplan-Meier survival was determined for all patients from the date of surgical intervention. Cox proportional hazards model analysis incorporating the variables of age, sex, histology, and stage estimated the effect of large cell neuroendocrine carcinomas and mixed large cell neuroendocrine carcinomas on recurrence and death. The stage of disease in all patients was assessed according to the 1997 American Joint Committee on Cancer guidelines. Results: Of the 2099 patients who underwent resection, 82 (3.9%) had large cell lung cancers. Perioperative mortality was 2.4%. Overall survival and freedom from recurrence at 5 years for the entire group was 47.1% and 58.4%, respectively. Overall survival by histologic subtype at 5 years was 30.2% for patients with large cell neuroendocrine carcinomas (n = 45), 30.3% for patients with mixed large cell neuroendocrine carcinomas (n = 11), and 71.3% for patients with large cell carcinomas (n = 21). Survival was significantly worse for patients with large cell neuroendocrine carcinomas than for patients with large cell carcinomas (P = .013). The presence of large cell neuroendocrine carcinomas in the specimen (the large cell neuroendocrine carcinoma and mixed large cell neuroendocrine carcinoma groups combined) was significantly associated with decreased survival (relative risk, 2.44; 95% confidence interval 1.29-4.58; P = .003) and decreased freedom from recurrence (relative risk, 4.52; 95% confidence interval, 1.76-11.57; P < .001). Conclusion: Patients with large cell neuroendocrine carcinomas have a significantly worse survival after resection than patients with large cell carcinomas, even in stage I disease. Accurate differentiation of large cell neuroendocrine carcinoma from large cell carcinoma is important because it identifies those patients at highest risk for the development of recurrent lung cancer.