Malignant melanoma of the skin is one of the most lethal cancers. The disease may spread either locally or regionally and to distant sites through predictable or unpredictable metastatic pathways. Accurate staging and restaging of disease are required for appropriate treatment decision making. Routine protocols based on clinical examinations and traditional radiologic evaluations are not cost-effective for the detection of systemic disease. In the last decade, nuclear medicine techniques, such as lymphoscintigraphy-directed lymphatic mapping and sentinel lymphadenectomy and (18)F-FDG PET, have played key roles in nodal and distant staging of melanoma. More recently, anatomic-functional imaging has been improved with the development of integrated PET/CT devices or combined SPECT/CT systems. (18)F-FDG-sensitive intraoperative probes have been specifically designed to detect small nodal and visceral metastases from melanoma and may become important tools for the cancer surgeon. In this article, we review the role of nuclear medicine in the assessment of malignant melanoma.