Background: Malignant Pleural Mesothelioma (MPM) is a highly aggressive tumor mainly associated with asbestos exposure. Aim: In this study we aimed to investigate the effect of asbestos on the gene expression profile of tight junction (TJ) components in patients with MPM. Materials and Methods: Gene expression data of claudins (CLDN) 1, 3-11, 14-18, occludin (OCLN) and Tight Junction Proteins (TJPs) 1-3 were analyzed from a study (Lopez-Rios et al. Cancer Res 2006; 66:2970-2979) comprising ofn=58 specimens of previously exposed to asbestos MPM patients and n=29 specimens of MPM patients that were unexposed. The gene expression data were log-transformed, median centered per array and the standard deviation was normalized to one per array. All values from the transformed data were downloaded from the OncomineCancer Microarray database(http://www.oncomine.org). Genes were considered differentially expressed when their fold change was significantly higher or lower between groups (p Results: We found that the CLDN15 gene is significantly under-expressed in patients that were previously exposed to asbestos as compared with the ones that were unexposed (p=0.004). In the former group of patients we observed a tendency for negative regulation of the TJP3 gene although no statistical significance was documented (p=0.057). Gene expression of CLDN 1, 3-11, 14, 16-18, OCLN and TJPs 1-2 was not influenced by asbestos exposure. Conclusions: These results are suggestive of the epigenetic effect of asbestos in the transcriptional level of the CLDN15 gene and provide indications for its potential utility as biomarker of risk for MPM.