The present study was a retrospective analysis of serum neuron-specific enolase (NSE) assayed in 302 patients with non-small cell lung cancer (NSCLC) before treatment. Serum NSE ranged from 0.6 to 183.0 ng/ml, with a mean value of 12.2 ng/ml, and exceeded 10 ng/ml in 145 patients (48.0%). The mean levels and rate of NSE positivity in 177 patients whose tumors were categorized as small, medium and large (from the product of the maximum and perpendicular axis of the tumor on chest X-ray), were highest in the large group. There was no significant relationship between serum NSE and the response rate to anticancer chemotherapy. The survival period of the patients with elevated serum NSE (median, 5.7 months) was significantly shorter, than those with normal serum NSE levels (median, 12.1 months). Serum NSE is of prognostic significance in a multivariate analysis (p < 0.01), but not predictive of response to chemotherapy in NSCLC.