There is a resurgence of interest in lymphoscintigraphy because of attention to the sentinel node concept and the availability of the surgical gamma probe that can be used in the operating room to localize radiolabeled sentinel nodes. Conventional surgical management of melanoma has been altered for intermediate thickness tumors such that lymph node dissection is performed for a lymph node bed only if the sentinel node is tumor positive on histological exam after gamma probe-guided excision. This approach is cost effective, saving about 80% of these patients (sentinel node tumor negative) the cost and morbidity of unnecessary "elective lymph node dissection." In addition, a biopsy can be performed on all lymph node beds that receive lymphatic drainage from the tumor site thereby improving staging and perhaps survival by providing the most appropriate therapy. Substantial work has been done to develop optimum imaging techniques and the best radiopharmaceutical preparation to achieve accurate, reproducible lymphatic drainage images. Our methodology includes the following intradermal injections of a technetium 99m sulfur colloid (modified preparation) are followed by dynamic imaging (10 seconds per frame); static imaging up to 30 minutes and late imaging at 1 to 2 hours. Images show lymphatic channels that lead to sentinel nodes in 1, 2, 3, or more anatomic locations. Surgical management is altered to include sampling sentinel nodes of nodal beds, many of which would not have been sampled by previous conventional surgical estimates of lymphatic drainage. While clinical success of lymphoscintigraphy and intraoperative probe localization of the sentinel node in melanoma is evident, use of lymphoscintigraphy and the sentinel node concept in breast cancer is investigative, but promising. The radiopharmaceutical is injected around the tumor in the breast followed by imaging to delineate lymphatic drainage to the sentinel node(s). Optimum methodologies for radiopharmaceutical, volume and/or activity of injectate, and imaging have yet to be determined. Breast lymphatic drainage can be to axilla, internal mammary, and/or supraclavicular nodes in any combination.