OBJECTIVES: Low dose computed tomography (CT) is the current recommended lung cancer screening modality for selected high risk population. The role of biomarkers is not clear. The objective of our study is to investigate the role of biomarkers in lung cancer screening via a systematic review and meta-analysis. METHODS: A systematic review is performed by reviewing primary studies focusing on biomarkers for lung cancer screening using the following keywords (lung cancer) AND ((screen*) OR (diagnosis) OR (diagnostic) OR (prediagnostic) OR (detection) OR (predict*) OR (development)) AND ((biomarker) OR (blood) OR (serum) OR (sera) OR (plasma) OR (antibodies) OR (urin*) OR (sputum) OR (exhale*) OR (volatile) OR (epithelium) OR (epithelial) OR (bronchial) OR (airway)) in the title/abstract in Pubmed® on December 31, 2011. We further limited our search to clinical trials, meta-analysis, or randomized controlled trials published for the past 5 years in English. Two independent reviewers identified studies compatible for selection criteria and data extraction after consensus was reached. Manual searching for relevant studies was also performed from relevant studies. A random effect model was used to calculate the pooled diagnostic performance of biomarker screening. RESULTS: Among the identified studies (n=172), three studies were included. In total, 1932 participants received various kinds of biomarkers screening. By using these biomarkers to differentiate cancer from non-cancer, the estimated pooled sensitivity and specificity with 95% confidence interval was 40% (24% ~ 57%) and 96% (94% ~ 97%) respectively. CONCLUSIONS: The diagnostic performance of biomarkers for lung cancer screening is fair based on very limited data as found in this systematic review. The role of biomarkers in lung cancer screening deserves further studies.