Initial reports suggest that positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) may offer greater diagnostic accuracy and versatility than conventional radiology in staging patients with metastatic melanoma. We reviewed the first 100 melanoma patients to have PET imaging at our institution. PET findings were correlated with all other available results, including plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging, bone scintigraphy, clinical findings and histopathology. A total of 415 metastatic lesions were evaluated, 388 (93%) of which were detected by PET. In 20 patients, PET detected 24 metastases up to 6 months earlier than conventional imaging or physical examination. Selection of surgical or medical management was specifically influenced by PET findings in 22 patients, and PET was used to clarify another 12 cases where CT was inconclusive. In nine patients undergoing chemotherapy, PET was used to assess response to treatment. We conclude that FDG-PET can accurately detect metastatic melanoma with a single non-invasive scan, and can demonstrate some metastases months before conventional imaging techniques. PET can improve the selection of patients for surgery, has potential for monitoring response to treatment and may prove a cost-effective means of staging melanoma patients.