As in squamous cell esophageal cancer, the presence and number of lymph node metastases constitutes the major prognostic factor in patients with adenocarcinoma of the distal esophagus (the so-called Barrett's cancer) who have had complete tumor resection (R0 resection). In contrast to squamous cell esophageal cancer, however, lymphatic spread in patients with Barrett's cancer appears to follow certain rules. Lymphatic spread is closely correlated with the pT category of the primary tumor; it starts only after infiltration of the basal membrane, and initially it is limited to the regional lymph nodes. Lymph node metastases at distant locations-i.e., the upper mediastinum and the celiac axis-are found almost exclusively in patients with multiple positive regional nodes. Skipping of regional lymph node stations occurs in less than 5% of the patients. These observations set the stage for individualized and tailored lymphadenectomy strategies. The sentinel lymphadenectomy concept may be applicable to patients with early Barrett's cancer.