Lung cancer is one of the most common fatal malignancies. Cyfra 21-1 is a tumor marker based on the determination of water-soluble cytokeratin 19 which is secreted by normal or malignantly transformed epithelial cells. It is suggested to be a valuable marker in the diagnosis of patients with lung cancer especially non-small cell type (NSCLC). This study was performed on 41 lung cancer patients, 19 patients with lung disease and 20 normal controls. Serum Cyfra 21-1 was measured by Enzyme Linked Immunosorbent Assay (ELISA). Serum Cyfra 21-1 was significantly increased in patients with lung cancer (p=0.000), especially in NSCLC (p=0.010) compared to SCLC. A significant positive correlation (r=0.506) was detected between serum CEA and serum Cyfra 21-1. Cyfra 21-1 showed a significant association (p=0.010) to lung cancer risk development in a logisitic regression analysis. Cyfra 21-1 is a tumor marker, with high sensitivity (82.5%) in NSCLC and is valuable in the diagnosis and differentiation of lung cancer.