PurposeThere is an obvious need to diagnose lung cancer using novel noninvasive and sensitive biomarkers. In this regard, the aim of the present study was to evaluate and compare sputum matrix metalloproteinase 2 (MMP‐2) in relation to serum MMP‐2 of lung cancer patients and other nonmalignant lung diseases in order to establish a new diagnostic and prognostic biomarker with a valid noninvasive technique.Experimental designGroup 1 included 32 newly diagnosed lung cancer patients and group 2 included 20 patients with benign pulmonary diseases. In addition, 38 healthy subjects served as control group. MMP‐2 activity levels were evaluated in serum and sputum samples of the studied groups using ELISA and zymography techniques.ResultsThere was a highly significant increase in serum and sputum MMP‐2 levels in malignant group in comparison with benign and control groups. In addition, there was a significant difference in the levels of serum and sputum MMP‐2 as regards the different histopathological types of lung cancer and advanced stages of lung cancer. Gelatin zymography was used to confirm the enzymatic activity of MMP‐2. A higher MMP‐2 activity was detected in lung cancer group in comparison with benign and control groups.Conclusions and clinical relevanceSerum and to a larger extent sputum MMP‐2 appear to be potential noninvasive markers for detecting lung cancer.