The feasibility of the sentinel node concept for malignancies originating in the alimentary tract is attracting much interest among researchers in the field of gastrointestinal oncology. We have tested more than 350 such cases and obtained favorable and promising initial results. The detectability of sentinel nodes using endoscopically injected Tc-99m tin colloid for these tumors exceeded 90%. Although the false negative ratio was not so low (approximately 10%), most of these cases had an inaccurate preoperative evaluation of mural invasion and/or a technically unfavorable injection. When the indication is restricted to patients with early-stage disease, and when the radioactive colloid is properly administered, sentinel node navigation therapy would be applicable for gastrointestinal malignancies. To achieve successful sentinel node navigation surgery it is essential to accurately identify sentinel nodes, and lymphoscintigraphy is a very useful test to confirm the location of sentinel nodes preoperatively. However, image processing is required for lymphoscintigrams because the original image depicts only high activity at the injection site and faint radioactivity in the sentinel nodes. We have clearly imaged the silhouette of the body using Compton scattered photons, and have also proposed several methods to improve the contrast between the injection sites and sentinel nodes. Many sentinel nodes can be clearly visualized by subtraction of the background activity with heterogeneous distribution. The development of the portable gamma camera, enabling intraoperative imaging, also contributes to less invasive biopsy of sentinel nodes. We have obtained promising initial results using a portable imaging device with semiconductor detectors. These promising results suggest that sentinel node navigation therapy including radiotherapy will be a new therapy for early-stage gastrointestinal malignancies in the near future, with nuclear medicine contributing to the establishment of new, less invasive therapies for gastrointestinal cancer.