Lung cancer is a lethal malignancy, however, no serum marker is routinely recommended till now. Prospectively two groups of patients included: Group I: Patients with advanced lung cancer. Group II: patients with benign lung disease as control. Serum Tissue Polypeptide Antigen (TPA) levels were measured by ELISA technique before the first line chemotherapy. The TPA cutoff taken was 1800 pg./ml. End points were comparison of high TPA in cases and controls and correlation between high TPA and disease progression (PD), progression free survival (PFS) and overall survival (OS). 30 patients with advanced lung cancer (16 non-small and 14 small cell lung cancer) and 15 patients with benign lung disease were included and followed up during the period from October 2008 to October 2011 with median follow-up of 1.5 years. High TPA was found in 50% of lung cancer cases compared to 26% in controls (p = 0.014). High TPA was found in 64% of cases showing PD versus 36% normal TPA (p = 0.08). 1 year PFS in high TPA was 32% versus 39% in normal TPA, (p = 0.2). 1 year OS in high TPA was 46% versus 73% in normal TPA (p = 0.6). Serum TPA is a potential marker for advanced lung cancer.