Summary The present study examines the relationship between neuroendocrine (NE) differentiation and the clinical behaviour of non-small cell lung cancer (NSCLC). Retrospective (n = 315) and prospective (n = 44) cohorts of non-small cell tumours were obtained from surgically treated cases of lung cancer, comprising 218 squamous cell carcinomas, 65 adenocarcinomas, 51 adenosquamous carcinomas, and 25 large cell undifferentiated carcinomas. Paraffin wax embedded and fresh frozen tissue sections were stained for the NE markers neurone specific enolase, creatine kinase-BB, bombesin, neurotensin, chromogranin A, synaptophysin and UJ-13A. The expression of two or more markers was observed in 30% of cases, and was taken to identify NE-NSCLC. A statistically significant correlation between nodal status and NE differentiation (P = 0.05), and disease stage and NE differentiation (P = 0.04) was observed. However, there was no correlation between NE differentiation and survival. These findings suggest that NE-NSCLC, analogous to SCLC is more highly metastatic than non-NE-NSCLC.