In our investigation, the optimal marker panel with NSE, CEA, and CYFRA21-1 can assist to the diagnosis of lung cancer, and SCCA + NSE + CEA can help in the diagnosis of AC; SCCA + CEA + CYFRA21-1 can aid to the diagnosis of SCC; and SCCA + NSE + CYFRA21-1 can assist in the diagnosis of SCLC. Here, ENO2 is linked to small cell lung carcinoma.