Background: Barrett's esophagus (BE) is a premalignant lesion of the esophagus characterized by intestinal metaplasia. it can progress to esophageal adenocarcinoma (EAC). Human epidermal growth factor receptor 2 (HER2) is a transmembrane receptor tyrosine kinase that regulates proliferation and differentiation. HER2 plays a role in the development of several types of cancer. Aim: This study aims to evaluate the role of HER 2 expression as a potential marker for the progression of Barrett's esophagus to esophageal adenocarcinoma and to examine its relationship with the clinic-pathological features of the patients. Material and Methods: This study included 40 subjects; 30 patients with gastro-esophageal reflux symptoms (23 patients with BE and 7 patients with EAC) and 10 normal subjects as a control group. Complete blood count and fecal occult blood test were measured. mucosal evaluation by upper endoscopy and histopathological examination of gastro-esophageal junction was done. Scoring of HER2 expression was performed by immunohistochemical staining. Results: HER2 expression was significantly increased in patients with BE and those with EAC. HER2 expression was significantly higher in tumorous tissue than in BE. HER2 expression was positively correlated with the degree of dysplasia in BE patients and with TNM stage in EAC patients. Conclusions: HER2 expression correlated well with the degree of dysplasia in BE and its progression to EAC. HER2 expression is a potential biomarker for early detection of EAC. HER2 expression may have a role in esophageal carcinogenesis. Further well-designed prospective studies are required to prove this hypothesis.