The Fibulins are a recently discovered family of extracellular matrix proteins. In this study, expression levels of the fibulin-2 (FBLN2) gene and its role in the formation of different metastatic foci were investigated in lung cancer patients. We analyzed 106 lung cancer patients and eight paraffin-embedded tissues, and 27 ethnical-, age- and sex-matched healthy controls for expression levels of the FBLN2 gene. cDNAs obtained from the enriched epithelial cells of peripheral blood lymphocytes and tumor tissues of patients were amplified with specific primers for the target FBLN2 gene and HPRT1 housekeeping gene using quantitative real-time polymerase chain reaction. FBLN2 gene expression levels of the enriched epithelial cells of peripheral blood lymphocytes were found to be decreased approximately twofold in all subsets of patients compared to healthy controls. Our results indicate a significant difference between patient subgroups and controls [F(4.124)=14.846, p0.05] among patient subgroups: bone metastases versus non-metastatic groups (p=0.997), bone versus brain metastases (p=0994), bone metastases versus two primary tumors (p=0.999), brain metastases versus two primary tumors (p=0.999), brain metastases versus non-metastatic (p=0.755), non-metastatic versus two primary tumors (p=0.996), non-metastatic versus all other metastatic patients (p=0.731). Moreover, we found a 50-fold upregulation of FBLN2 gene expression in paraffin-embedded tissues compared with the enriched epithelial cells ofperipheral blood lymphocytes of patients. In the study, the enriched epithelial cells of peripheral blood lymphocytes of decreased FBLN2 expression was found to be correlated with metastasis. The fibulin-2 molecules might induce the metastatic potential through interaction with the other molecules in the microenvironment, nevertheless, it is needed further research whether the importance of FBLN2 on lung cancer oncogenesis and as a biomarker for metastatic lung cancer.