Objective The Barrett`s multistage process is characterized histopathologically by progression from Barrett`s intestinal metaplasia to Barrett`s esophagus with dysplasia and ultimately adenocarcinoma. Understanding of the molecular alterations in this multistage process may contribute to improved diagnosis and treatment. Retinoid X Receptors (RXR) play an important role in regulating the morphogenesis, development, growth, and differentiation of cells. Alterations in RXR expression have been observed in a variety of solid tumors, however the role in Barrett`s esophagus disease has yet to be determined. Aim of this study was to assess the prevalence and timing of RXR mRNA expression in Barrett`s metaplasia-dysplasia-adenocarcinoma sequence and to determine its role for the development and progression of this disease. Methods We analyzed the mRNA expression of all 3 RXR subtypes (RXR-alpha, RXR-beta, RXR-gamma) by using a quantitative real-time RT-PCR method (Taqman) in 108 specimens from 19 patients with Barrett`s esophagus without carcinoma (BE-group), 20 patients with Barrett`s associated adenocarcinoma (EA-group), and a control group of 10 patients without evidence of gastro-esophageal reflux disease (CG). Results RXR-alpha mRNA expression was significantly decreased (p<0.001; Kruskal-Wallis test), and RXR-gamma (p<0.001) was significantly increased at higher stages in Barrett`s esophgus disease. RXR-beta expression was highest in Barrett`s tissues and significantly increased compared to normal squamous tissues (p=0.01, Wilcoxon test) and adenocarinoma tissues (p=0.018, Mann-Whitney test). RXR-alpha and RXR-beta mRNA expression were significantly associated in normal squamous esophagus tissues (r2=0.49; p<0.001; Spearman test), Barrett`s tissues (r2=0.63; p<0.001), and adenocarcinoma tissues (r2=0.68; p=0.001). There were significant differences in RXR-alpha (p=0.011) and RXR-beta (p=0.005) mRNA expression in histopathologically normal squamous esophagus tissues in patients with cancer and the normal control group(CG). Conclusions These findings suggest that alterations in the mRNA expression of all 3 RXR subtypes are frequent events in the development and progression of Barrett`s esophagus and associated adenocarcinoma, that quantitation of RXR mRNA expression may be useful biomarkers for this disease, and that a widespread field-effect is present in the normal esophagus of patients with esophageal adenocarcinoma.