We recruited 805 patients with suspicious pulmonary masses that were identified finally as lung cancer or benign pulmonary masses. The serum levels of four tumor markers, including squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (Cyfra21-1) and neuron specific enolase (NSE) were tested for every patient. Though receiver operating characteristic (ROC) curves indicated unsatisfactory diagnostic power of those four tumor markers for lung cancer, 37.3% of early-staged lung cancer could be diagnosed just on the combination assays of the four tumor markers, under adjusted cut-off values through our statistical analysis retrospectively.