Abstract: Objective To determine the cut-off value of serum neuron-specific enolase (NSE) level for distinguishing small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Methods Serum NSE levels were measured by enzyme-linked immunosorbent assay in 137 patients with NSCLC or SCLC, and the best cut-off value was analyzed using ROC curve. Results The positivitity rate of serum NSE was significantly higher in patients with SCLC than in those with NSCLC (P<0.01). The best cut-off value was 15.45 μg/L using ROC curve, which gave a sensitivity of 66.7% and specificity of 65.7%. Conclusion Serum NSE level may allow simple and cost-effective differentiation of SCLC and NSCLC.