A patient with Barrett's esophagus and high grade dysplasia is presented. He underwent a fundoplication and, subsequently, nearly three years of high-dose proton pump inhibition therapy. At the time of esophagogastrectomy, extensive squamous re-epithelialization was observed along with two histologic foci of intramucosal adenocarcinoma. Despite partial regression of Barrett's esophagus, high grade dysplasia present for more than 4 years had progressed to adenocarcinoma. Partial squamous repopulation of Barrett's esophagus is an inadequate endpoint of therapy. Complete regression is necessary to eliminate the risk of cancer.