FBLN-3 has been identified as an antagonist of angiogenesis which modulates cell morphology, growth, adhesion, and motility. In the present study, we investigated the promoter methylation status of FBLN-3 gene in non-small cell lung carcinoma (NSCLC) by methylation-specific PCR and analyzed its correlation with clinicopathological factors. The methylation of FBLN-3 gene promoter was detected in 28 of 65 (43.1%) NSCLC tissue samples and 6 of 65 (9.2%) corresponding non-tumor tissue samples (P< 0.05). The methylation of FBLN-3 gene promoter led to the loss of FBLN-3 gene expression in NSCLC. Additionally, FBLN-3 promoter methylation was observed to be correlated with relative poor differentiation, advanced pathological stage and lymph node metastasis of NSCLC patients (P=0.017, 0.0057 or 0.002, respectively), but not with gender, age, histological type, and smoking condition (P>0.05). These results indicated that the loss of FBLN-3 gene induced by promoter methylation might play important roles in the progression of NSCLC and FBLN-3 promoter methylation might be a promising biomarker for early detection of NSCLC. © 2009 Elsevier Ireland Ltd.