Pancreatic and esophageal cancers are both gastrointestinal malignancies with relatively low long term survival. In part, the aggressiveness of these tumors is related to local and distant metastatic potential, subsequently affecting prognosis and treatment modalities. Currently, the mainstay of staging involves in-depth radiographic imaging with surgery offered for potentially curative tumors. As a result, staging becomes a key determinant in the role of surgical resection. As minimally invasive approaches continue to gain popularity, the idea of natural orifice surgery has been raised as a possible adjunct to staging neoplasias. Currently, the insertion of a perioral endoscope to gain access to the peritoneal cavity via a transgastric incision has been investigated, with demonstration of feasibility and efficacy in several animal studies and limited clinical studies. Similar techniques have been employed to gain access to the thoracic cavity via a transesophageal incision in early animal studies. This article aims to outline the advantages and limitations of natural orifice endoscopic surgery, and review the use of endoscopic techniques to assess the intraperitoneal cavity via a transgastric incision for determining local and widespread metastases with reference to pancreatic carcinoma. The method of transesophageal staging for esophageal carcinoma will also be discussed.