To assess the prognostic value of pretreatment serum neuron-specific enolase (NSE) in nonsmall cell lung cancer (NSCLC), levels were measured in 84 NSCLC patients, 40 healthy controls, and 20 patients with benign pulmonary diseases. NSE concentration was higher in NSCLC (11.7 +/- 10.8 ng/ml) (mean +/- SD; median = 9.7 ng/ml) than in the two control groups (p < 0.001). Serum NSE was neither related with the tumor-node-metastasis (TNM) stage, nor with histologic subtype. At a cutoff value of 15 ng/ml, NSE had a sensitivity of 27.3% and a specificity of 96%. Patients with a preoperative NSE level < 15 ng/ml showed significantly longer 24-month survival than those whose initial levels were > 15 ng/ml (70 vs, 47%; p < 0.05), and this was confirmed after stratifying by TNM stage. Likelihood of tumor relapse in I, II, and IIIa TNM stages showed similar behavior. These findings suggest that NSE could be used as an adjunctive prognostic test in NSCLC patients.