Introduction: The earlier diagnosis of adenocarcinoma is associated with higher cure rate. Identification of biomarkers might provide a better understanding of the process of malignant transformation and helps to identify early markers of malignant transformation in Barrett's esophagus, a known pre-malignant lesion.Aim: To investigate the role of glutathione S-transferase P1 (GSTP1) and matrix metalloproteinase-9 (MMP-9) expressions in the development and progression of reflux esophagitis-Barrett’s esophagus-dysplasia-adenocarcinoma sequence in the esophagus.Methods: The tissue expression of both GSTP1 and MMP-9 were analyzed in a total of 120 paraffin-embedded esophageal samples by immunohistochemistry including patients with reflux esophagitis (n= 15), Barrett’s esophagus (n= 15), esophageal adenocarcinoma (n= 15), and a control group without any histological changes (n= 15). Immunostaining was determined semiqualitatively and compared in the different groups.Results: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to all other groups. No major changes were observed between Barrett's esophagus without dysplasia and reflux esophagitis. Barrett with concomitant dysplasia and adenocarcinoma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett with concomitant dysplasia. Simultaneous alterations of GST and MMP-9 were inversely correlated (r = - 0.76) in all patients.Conclusion: The disturbed balance between GSTP1 and MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggests their association with esophageal carcinogenesis. Loss of GST and gain of MMP-9 in Barrett with dysplasia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esophagus might be useful to identify patients at higher risk for progression to cancer.