In Barrett's cancer, the frequency of lymph node metastases to the middle and upper mediastinum has rarely been analyzed because it requires a complete mediastinal lymphadenectomy. Fifty-one patients with esophageal adenocarcinoma underwent transthoracic en-bloc esophagectomy with two-field lymph node dissection. A meticulous work-up of the resected specimen allowed a specific assignment of each single lymph node to defined groups of the abdominal and mediastinal compartment. Histopathology classified the lymph nodes as metastatic or nonmetastatic. A total of 1706 lymph nodes were resected, with a mean of 33.5 lymph nodes per patient (range, 13-74). Of 51 patients, 28 (54.9%) were classified as pN1; 7 (25%) of 28 pN1 patients had nodal metastases at the level of the tracheal bifurcation (3 of 28 patients) or in the upper mediastinum (5 of 28 patients). In all 28 pN1 patients, the abdominal compartment was involved. The distribution of nodal metastases demonstrated that the main lymphatic spread occurred close to the primary tumor, along the lesser curvature and the left gastric artery. Adenocarcinomas of the distal esophagus have a bidirectional lymphatic spread to the mediastinum and the abdomen. Two-field lymphadenectomy seems to be an adequate surgical approach for this tumor entity to achieve a complete nodal clearance.