Background: Chronic gastritis and esophagitis are associated with changes in mucosal glycosylation patterns. Lectins represent a group of specific carbohydrate binding proteins that can be used as sensitive tools for the analysis of glycosylation patterns. Aim: To investigate the binding patterns of lectins Ulex europaeus agglutinin-I (UEA-I), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA) and peanut agglutinin (PNA) at the gastroesophageal junction in nonerosive (NERD), erosive reflux disease (ERD) and Barrett’s esophagus (BE). Methods: One hundred and twenty-two patients (female n = 53; male n = 69; controls n = 28; NERD n = 36; ERD n = 24 and BE n = 34) were included in this study. The binding patterns of lectins were examined immunohistochemically at the squamocolumnar junction, in squamous epithelium and columnar-lined epithelium. Staining patterns of lectins were semiquantitatively evaluated using an immunohistochemical score and the data were analyzed using non-parametric tests. Results: BE, as compared to the controls, was associated with specific lectin-binding patterns: lectin binding of UEA-I and DBA were significantly decreased at the superficial (p = 0.012; p = 0.00036, respectively) and at the deep glandular body (p = 0.045; p = 0.055, respectively). Comparisons of lectin-staining scores between GERD and BE revealed significant increases of UEA-I in both the stratum superficiale (p = 0.0155) and stratum spinosum (p = 0.0048) of SE in patients with BE. Notable, this change was specific for patients with BE, while no difference was observed between patients with GERD and controls. Conclusion: We found two major types of lectin-binding patterns. First, lectin-binding characteristics associated with GERD in general, and second, lectin-binding patterns which were specific for BE. Lectin UEA-I-binding proteins were specifically increased in the squamous epithelium of patients with BE. Thus, UEA-I may serve as a potential marker for BE, especially in patients with short segment BE.