Neuron-specific enolase (NSE) is a specific tumor marker in small cell lung cancer (SCLC) patients, however, it has been reported that serum NSE levels are elevated in some patients with non-small cell lung cancer (NSCLC). To determine the most suitable cut-off level to distinguish between these two types of cancers, NSE levels were measured on serum samples of 417 patients with lung cancer without clinical information. Receiver operating characteristic (ROC) curve showed 14.5 ng/ml as a cut-off level and the 95 percentile serum NSE level in NSCLC was 20.5 ng/ml. None of the NSCLC patients had serum NSE levels more than 70 ng/ml. The measurement of serum NSE provides a discrimination between NSCLC and SCLC. If an NSCLC patient presents with a NSE level >20.5 ng/ml, pathological features must be examined with regard to the neuroendocrine differentiation.