Objective To investigate the diagnostic value of combined detection of serum tumor markers,including CEA,CA125,neuron-specific enolase (NSE) and cytokeratin fragment antigen 21-1 (CYFRA21-1) for lung cancer patients.Methods The subjects involved 138 diagnosed lung cancer patients (82 males,56 females,average age 58.6 years,from October 2010 to March 2012),96 patients with benign lung diseases (56 males,40 females,average age 51.3 years) and 45 healthy adults (30 males,15females,average age 43.9 years).The pathological types of lung cancer consisted of 66 squamous cell carcinoma (SCC),52 adenocarcinoma and 20 small cell lung cancer (SCLC).The serum levels of CEA,CA125,NSE and CYFRA21-1 were measured with electrochemiluminescence immunoassay.The diagnostic efficacy for different pathological types was compared among each single tumor marker and combination of tumor markers.One-way analysis of variance q test were used for statistical analysis.Results The serum levels of CEA,CA125,NSE and CYFRA21-1 in patients with lung cancer were higher than those in patients with benign lung diseases and in healthy subjects (CEA:(19.99±30.99),(10.78±19.77),(3.25±3.42) μg/L;CA125:(79.70±95.98),(44.96±44.97),(20.66±7.13) μg/L; NSE:(35.23±40.22),(15.31±8.42),(13.30±5.65) μg/L; CYFRA21-1:(18.07±43.71),(8.30±8.83),(3.13±1.60) μg/L; F=4.481,5.436,4.776,6.002,all P<0.05).The highest level of CEA,NSE or CYFRA21-1 were found in adenocarcinoma (F=4.932,P<0.05),SCLC (F=5.119,P<0.05) or SCC (F=5.378,P<0.05),respectively.The highest sensitivity tumor markers for SCC,SCLC and adenocarcinoma were CYFRA21-1 (78.8%,52/66),NSE (75.0%,15/20) and CEA (57.7%,30/52),respectively.In combined detection,the highest sensitivity combinations for SCC,SCLC and adenocarcinoma were CEA+CYFRA21-1+NSE (89.4%,59/66),CEA+CYFRA21-1+NSE (80.0%,16/20) and CEA+CA125+NSE (78.8%,41/52),respectively.Conclusions Combined detection of serum tumor markers is more sensitive for the diagnosis of lung cancer.The expressions of the above four tumor markers is correlated with pathological types of lung cancer. Key words: Lung neoplasms ; Carcinoembryonic antigen ; Antigens, tumor-associated,carbohydrate ; Phosphopyruvate hydratase ; Keratins