BACKGROUND: Lung cancer is the most lethal malignant neoplasm in the world. Serum cytokeratin fragment 21-1 (Cyfra 21-1) is a valuable tumor marker for detection of lung cancer, and it has good sensitivity and specificity. The aim of this study was to investigate the diagnostic value of Cyfra 21-1 levels in patients with lung cancer. METHODS: We retrospectively reviewed 814 samples from 169 patients with lung cancer, 124 patients with benign pulmonary diseases, and 521 normal controls from health check-up clinic. Serum Cyfra 21-1 levels were determined with Architect CYFRA 21-1 kit (Abbott, USA) using Architect i2000 analyzer. RESULTS: Median levels and interquartile ranges for Cyfra 21-1 in patients with lung cancer (non-small cell lung cancer: 3.16 [1.98, 9.00] ng/mL, small cell lung cancer: 3.32 [2.07, 5.20] ng/mL) were higher than those in patients with benign pulmonary diseases (1.50 [1.17, 2.17] ng/mL; P<0.01) and in normal controls (1.26 [0.93, 1.75] ng/mL; P<0.01). Sensitivity, specificity, positive predictive value, and negative predictive value for Cyfra 21-1 were 70.4%, 81.2%, 49.6%, and 91.3%, respectively. The area under the curve for Cyfra 21-1 was 0.839 (95% confidence interval, 0.802-0.877). CONCLUSIONS: We concluded that Cyfra 21-1 may be useful in the diagnosis of lung cancer.