We performed a pooled analysis of the efficacy of serum neuron-specific enolase (NSE) levels for early detection of small cell lung cancer (SCLC) in patients with benign lung diseases and healthy individuals. Comprehensive searches of several databases through September 2016 were conducted. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Ultimately, 33 studies containing 9546 samples were included in the review. Pooled sensitivity of NSE for detecting SCLC was 0.688 (95% CI: 0.627-0.743), specificity was 0.921 (95% CI: 0.890-0.944), positive likelihood ratio was 8.744 (95% CI: 6.308-12.121), negative likelihood ratio was 0.339 (95% CI: 0.283-0.405), diagnostic odds ratio was 25.827 (95% CI: 17.490-38.136) and area under the curve was 0.88 (95% CI: 0.85-0.91). Meta-regression indicated that study region was a source of heterogeneity in the sensitivity and joint models, while cut-off level was a source in the joint model. Subgroup analysis showed that enzyme linked immunosorbent assays had the highest sensitivity and radioimmunoassay assays had the highest specificity. The diagnostic performance was better in Europe [sensitivity: 0.740 (95% CI: 0.676-0.795), specificity: 0.932 (95% CI: 0.904-0.953)] than in Asia [sensitivity: 0.590 (95% CI: 0.496-0.678), specificity: 0.901 (95% CI: 0.819-0.948)]. In Europe, 25 ng/ml is likely the most suitable NSE cut-off level. NSE thus has high diagnostic efficacy when screening for SCLC, though the efficacy differs depending on study region, assay method and cut-off level. In the clinic, NSE measurements should be considered along with clinical symptoms, image results and histopathology.