Background & aim: Due to the fact that lung cancer is the most common cause of cancer-related deaths worldwide, identification of biomarkers is of great importance for early detection. One of molecules which may be used as a diagnostic biomarker is Threose Phosphate Isomerase (TPI). The purpose of this study was to evaluate serum levels of Threose phosphate isomerase in patients with lung cancer. Methods: In this case-control study, 50 males with a mean age of 65.1±11.4 were included. Twenty-seven patients had squamous cell carcinoma, seven had small cell carcinoma and 16 had adenocarcinoma respectively. Meanwhile, 38 healthy men (mean age 65.1±11.4) were selected as the control group. ELISA technique was used to measure the TPI. Collected data were analyzed using ANOVA and t-test. Results: TPI serum levels of patients were not statistically significant compared with the control group (p =0.76). Moreover, a separate analysis of sub groups of lung cancer demonstrated that serum levels of TPI in the sub group of lung cancer group compared with the control group had no significant difference. Conclusions: No correlation between serum levels of TPI and lung cancer was observed. It probably indicated the TPI role in different types of cancer and its geographical distribution in human populations.