Malignant melanoma can metastasize to almost any organ site. Optimal management requires sensitive radiographic evaluation of the entire body. The optimal management of patients with metastatic melanoma requires accurate assessment of extent of disease (EOD). The objective of this study was to evaluate the accuracy of fluorine-18 deoxyglucose (FDG) whole-body positron emission tomography (PET) in determination of EOD in patients with metastatic melanoma and its impact on surgical and medical management decisions. Forty-nine patients (30 men, 19 women; aged 25-83 years) with known or suspected metastatic melanoma underwent EOD evaluation using computerized tomography (CT) of the chest, abdomen, and pelvis, and magnetic resonance imaging (MRI) of the brain. After formulation of an initial treatment plan, the patients underwent FDG-PET imaging. The EOD determined by PET was compared with physical examination and conventional radiography findings. Fifty-one lesions were pathologically evaluated. The impact of PET on patient management was assessed based on the alterations made in the initial treatment plan after reevaluation of the patients using the information obtained by PET. The PET scan identified more metastatic sites in 27 of 49 (55%) of the patients who had undergone a complete set of imaging studies, including CT scans of the chest, abdomen, and pelvis, and MRI of the brain. In 6 of those 27 patients, PET detected disease outside the fields of CT and MRI. Fifty-one lesions were resected surgically. Of these, 44 were pathologically confirmed to be melanoma. All lesions larger than 1 cm (29 of 29) were positive on PET, whereas only 2 of 15 (13%) lesions smaller than 1 cm were detected by PET. The results of PET led treatment changes in 24 patients (49%). Eighteen of these changes (75%) were surgical. In 12 cases (67%), the planned operative procedure was cancelled, and in 6 cases (33%), an additional operation(s) was performed. In 6 of 24 (25%) patients, biochemotherapy, radiation therapy, or an experimental immunotherapy protocol was prompted by identification of new foci of disease. Compared with conventional imaging, FDG-PET provides more accurate assessment of EOD in patients with metastatic melanoma. Significant surgical and medical treatment alterations were made based on PET results.