The incidence of adenocarcinoma of the esophagus is rising rapidly in Western Europe and North America. It is an aggressive disease with early lymphatic and hematogenous dissemination. TNM cancer staging systems predict survival on the basis of the anatomic extent of the tumor. However, the adequacy of the current TNM staging system for adenocarcinoma of the esophagus or gastroesophageal junction (GEJ) is questioned repeatedly. Numerous prognostic factors have been described, but are not included in the TNM system. This review describes clinical parameters, aspects of operative technique, response to preoperative chemoradiotherapy therapy, complications and established pathologic determinants found in the resection specimen that have a prognostic impact. Furthermore, their potential application in the clinical setting in patients with adenocarcinoma of the esophagus or GEJ is discussed. Future directions to improve staging systems are given.