Background: In most patients with Barrett's esophagus (BE), endoscopic surveillance for early detection of dysplastic or neoplastic changes depends on the results of forceps biopsy. Endoscopic mucosal resection (EMR) is rapidly growing as an excellent diagnostic and therapeutic method for BE with dysplastic and early neoplastic changes. It is not entirely clear what is the agreement between the histopathologic diagnosis based on biopsy specimen versus that based on mucosal resection specimen. Objective: The aim of this study was to check the accuracy of biopsy for precise histopathologic diagnosis of dysplasia and neoplasia, compared to EMR in patients with BE and its related superficial esophageal lesions. Methods: During the period from December 2011 to December 2013, 24 patients with previously diagnosed BE (18 men, 6 women, mean age 49.75 ± 13.3 years, range 32-83 years) underwent routine regular surveillance endoscopic examination. Targeted biopsies were taken from the visible lesions in 12 patients with macroscopically suspicious lesions of the esophagus (group 1), and 4 quadrant biopsies were taken from BE segments in 12 patients without visible lesions (group 2). Then EMR was performed within 3 weeks, in all patients. Results: Initial histopathologic diagnosis of biopsies were: non dysplastic BE (NDBE) in 11 cases, low-grade dysplasia (LGD) in 7 cases, high-grade dysplasia (HGD) in 4 cases, intramucosal carcinoma (IMC) in one case, and invasive adenocarcinoma (IAC) in one case. EMR based diagnosis was identical with biopsy based diagnosis in only 14 cases (58.33%). The diagnosis differed in 10 cases (41.67%); 9 of them (37.5%) had "Upgrading" (i.e. diagnosis towards a higher degree of dysplasia) of biopsy based diagnosis in comparison to EMR based diagnosis, while, only one case (4.17%) had "Downgrading" (i.e. diagnosis towards a lower degree of dysplasia) of biopsy based diagnosis in comparison to EMR based diagnosis. Conclusions: Endoscopic biopsy is not a satisfactory method for accurate diagnosis of esophageal dysplastic or neoplastic changes in BE patients with or without suspicious superficial lesions. EMR should therefore be the preferred diagnostic method in such patients.