This review focuses on the histopathological evaluation of endoscopic mucosal resection (EMR) specimens in Barrett's esophagus, and on the histopathological, biological, and molecular properties of postablation Barrett's esophagus. EMR may be used for both diagnostic and therapeutic purposes. Diagnostic accuracy regarding the grade and stage of neoplasms is improved with the use of EMR, but the value of this technique for treatment is more controversial because of the high prevalence rate of positive margins and the rate of metachronous lesions found elsewhere in the esophagus during follow-up. Ablation techniques, such as argon plasma coagulation, photodynamic therapy, and radiofrequency ablation, are used increasingly for the treatment of Barrett's esophagus and related neoplasms, often in combination with EMR. A common problem after use of these techniques is the development of islands of neosquamous epithelium (NSE) which can overlie buried Barrett's (and/or dysplasia) epithelium. This is, therefore, concealed to the endoscopist's view and may be allowed to progress to cancer without detection. NSE is histologically similar to normal esophageal squamous epithelium and does not possess the molecular aberrations characteristic of Barrett's esophagus. In contrast, residual nonburied Barrett's esophagus shows persistent pathologic and molecular abnormalities and may progress to cancer upon long term follow-up. The biological potential and rate of progression of nonburied residual Barrett's esophagus following ablation is unclear, but some preliminary studies suggest that the risk may decrease. Buried nondysplastic Barrett's esophagus appears to show decreased biological potential and this may be related to protection from the contents of the lumen by the barrier function of the overlying NSE. On the other hand, anecdotal reports have suggested that buried dysplasia may progress to cancer in some instances.