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Introduction: Bronchogenic carcinoma is a leading cause of cancer-related death in men and women. Early diagnosis and treatment in these cases are essential for a better prognosis. Serum biomarkers such as serum amyloid A (SAA) and CYFRA 21-1 have generated encouraging results regarding their use in the diagnosis of these cases but data on their role in the Indian scenario are still lacking. Aim: The study aims to measure the levels of SAA and CYFRA 21-1 in various types of lung cancer and compare them with patients without lung cancer. It also aims to compare the values of these biomarkers before and after chemotherapy and correlate them with response to treatment. Materials and Methods: It was a prospective, case--control study conducted in the Department of Pulmonary Medicine, Government Medical College, Chandigarh. All histologically and/or cytologically proven lung cancer cases were included in the study group while patients with diseases other than lung cancer formed the control group. All patients were evaluated through a complete history and thorough clinical examination. Measurement of SAA and CYFRA 21-1 in blood was done by sandwich ELISA method. The patients in the study group were followed up regularly and the biomarkers were measured again after four cycles of chemotherapy. The response of tumors to chemotherapy was evaluated as per modified Response Evaluation Criteria in Solid Tumors criteria. The statistical analysis was carried out using SPSS version 19.0. Results: The study group and control group included 20 patients each. Hoarseness of voice and hemoptysis were significantly associated with lung cancer patients (P = 0.001 and P = 0.025, respectively). Serum levels above 8745 ng/ml for SAA and 2.55 ng/ml for serum CYFRA 21-1 were used as diagnostic biomarker in lung cancer. The serum levels of CYFRA 21-1 were found to be significantly raised in nonsmall cell carcinoma (NSCLC) in comparison to SCLC of lung. There was a statistically significant decrease in the serum levels of CYFRA 21-1 in lung cancer patients on C4 cycle of chemotherapy in comparison to C1 cycle (P = 0.014). Conclusion: SAA and CYFRA 21-1 could be valuable diagnostic biomarkers in lung cancer. CYFRA 21-1, in addition, could also be used as prognostic biomarker in lung cancer patients undergoing chemotherapy as it showed significant decrease after C4-cycle of chemotherapy. It can also be a potential biomarker to differentiate small cell and NSCLC. [ABSTRACT FROM AUTHOR]