The main principles for optimal management of HGD arising in Barrett's esophagus are that unequivocal diagnosis of HGD is a prerequisite for making the decision of any kind of treatment. HGD must be resected because of the presence of neoplastic cells in the lamina propria in 40% of patients. No reliable endoscopic or endosonographic feature exists that allows accurate prediction of the existence of neoplastic cells within the lamina propria of a patient having HGD in endoscopic biopsy material. Prompt decision to remove an HGD lesion as soon as unequivocal histologic diagnosis has been settled prevents the development of extraesophageal neoplastic spread. Esophagectomy is preferable to endoscopic mucosal excision because approximately 20% of patients who have HGD in preoperative biopsy material carry neoplastic cells beyond the muscularis mucosae. Esophagectomy can be limited to the removal of the esophageal tube without extended lymphadenectomy because 96% of patients who have HGD in endoscopic biopsy samples have a neoplastic process confined to the esophageal wall. Esophageal resection must encompass all the Barrett's area because of the risk for the further development of a second cancer in the metaplastic remnant. Vagus-sparing esophagectomy with colon interposition or elevation of the antrally innervated stomach up to the neck is preferable to conventional esophagectomy with gastric pull up because the former procedure maintains gastric function intact, whereas the latter exposes patients to the risk for the long-term development of reflux esophagitis and even of metaplastic transformation of the proximal esophageal remnant. Subtle details in the understanding of a given patient's clinical course may be critical for making the decision of the most relevant mode of therapy; therefore, patients who have HGD should be treated in dedicated centers, the experience of which offers the best chances of uneventful recovery if the surgical option is retained.