Background: Over the past two decades the management of esophageal cancer has changed from the treatment of patients with advanced staged squamous cell cancers to those with earlier staged adenocarcinoma occurring in the setting of Barrett’s esophagus. A number of new unproven therapeutic approaches have been developed and used in patients with early asymptomatic tumors detected in the course of Barrett’s surveillance; such as mucosal ablation or endoscopic mucosal resection. For patients with more advanced staged tumors, combined modality therapy (neoadjuvant chemo-radiotherapy) has been broadly applied, despite the lack of clear evidence regarding the superiority of this approach. Methods: Our experience with 100 consecutiveen bloc resections performed as primary therapy for esophageal adenocarcinoma and data from the literature are reported. Results: Theen bloc resection has a low incidence of local recurrence within the operative field even when multiple nodes are involved. Overall five-year survival was 52 % with a 39 % survival for patients with lymph node metastases and tumors that extend into the muscularis propria and beyond. We have found that the presence of more than 4 involved nodes, or a lymph node ratio of >10 % identifies patients with an 80 % or more risk of developing systemic metastases. When the endoscopic ultrasound suggests that a tumor extends into but is limited to the submucosa, 19 % of the patients will have lymph node metastases, with only 3 % having more than 4 nodes involved. Invasion of the muscularis propria or beyond is associated with lymph node involvement in 75 % to 85 % of patients. Conclusions: An extended transhiatal resection, including a complete lymphadenectomy of the upper abdominal region, and lower mediastinum performed through an enlarged hiatus, would be adequate for complete removal of all disease in 97 % of patients with tumor penetration limited to the submucosa. For patients with tumors that extend into the muscularis propria and beyond, a systematic abdominal and thoracic lymph node dissection should be performed to maximize the chances of a complete (R0) resection. In this situation, a transthoracic exposure is necessary to perform an adequate mediastinal lymph node dissection. The number or ratio of lymph node metastases is directly related to the risk of developing systemic metastases following complete resection. This concept can be used as an indicator for postoperative adjuvant therapy.