Barrett’s esophagus (Barrett’s esophagus) is the pre-malignant lesion for the majority of patients with esophageal adenocarcinoma. The sequence of events from Barrett’s esophagus to adenocarcinoma has several steps, encompassing low grade intra-epithelial Neoplasia (LGIN), and high grade intra-epithelial neoplasia (HGIN). As it seems that this evolution spans many years, endoscopic surveillance for patients with Barrett’s esophagus has been advocated, to detect neoplasia at early and curable stages. In recent years endoscopic imaging techniques have improved greatly. However, even using sophisticated imaging techniques, the standard approach of comprehensive endoscopic biopsy protocol includes direct sampling from suspicious areas in combination with systematic random four quadrant biopsies (4QBs) every 1±2 cm along the length of the Barrett’s segment, according to the Seattle protocol, is recommended as the gold standard for surveillance. The approach is labor-intensive but iscurrently considered to be the state of the art. However, the primary problem is the inter-operative re-localization of these biopsy sites to guide the treatment. Often re-localization is performed using the markings made on the endoscope which are highly unreliable and prevent targeted treatments.