In recent months, we have witnessed a 'paradigm shift' in the management of intermediate-thickness melanoma. The collective experience of the recent past confirms the validity of the 'sentinel' lymph node as being the initial draining site from a specific area of skin. Furthermore, the sentinel lymph node has been confirmed as the most likely site in the regional lymph node basin to harbor occult metastatic disease. Identification of sentinel lymph nodes by visual inspection and intraoperative gamma probe detection after the peritumoral injection of Lymphazurin blue dye and technetium sulfur colloid is a reliable new technique. Staging accuracy also has improved, allowing the precise identification of patients who benefit from avoiding the morbidity of radical lymphadenectomy. The importance of accurate staging has been heightened by data demonstrating effective adjuvant therapy with recombinant interferon-alpha 2B. Precisely defining patient subsets who benefit from adjuvant high-dose interferon-alpha 2B is the current focus of clinical trials designed to maximize the enhanced staging accuracy of the novel approach of sentinel lymph node biopsy.