The role of the homeobox genes Backfoot (BFT) and caudal-related Homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The goal of this study was to investigate the mRNA expression of BFT and CDX2 in NSCLC and to determine the association with the pathogenesis and the potential as a biomarker of this disease.The mRNA expression of BFT and CDX2 was analyzed by quantitative real-time RT-PCR in the tumor and matching normal tissue from 23 patients with NSCLC.The mRNA expression was detectable with the following frequencies in the tumor (t) and normal (n) tissues: BFT=100% (n), 100% (t); CDX2=100% (n), 100% (t). The median CDX2 mRNA expression was 0.85 (range: 0.01-15.47) in the tumor tissue and 0.045 (range: 0-1.36) in the matching normal lung tissue (p=0.001). The median BFT mRNA expression was 0.0034 (range: 0-0.35) in the tumor tissue and 0.0001 (range: 0-0.10) in the matching normal lung tissue (p=n.s.). There were no associations between the mRNA expression levels of BFT and CDX2 and clinicopathological variables.The mRNA expression of the homeobox genes is detectable at a high frequency in the tumor and normal tissue of patients with non-small cell lung cancer. Up-regulation of CDX2 mRNA expression appears to be associated with the pathogenesis of this malignant disease. The quantification of CDX2 and BFT mRNA expression in lung tissue is a potential biomarker for the identification of patients at risk of the development of NSCLC.