To assess the feasibility and accuracy of positron emission tomography (PET) in the detection of metastatic malignant melanoma, the authors studied 12 patients approximately 1 hr following a 10-mCi injection of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). Scan findings were compared to physical examination, imaging and biopsy results. For intra-abdominal visceral and lymph node metastases, the sensitivity of FDG-PET was 100% (15/15). PET also identified three metastatic foci noted only retrospectively on CT, and two metastatic foci seen only on follow-up CT several months later. Eight additional intense foci of FDG uptake that were seen on PET have not yet been confirmed as tumors. In superficial lymph nodes, PET correctly identified seven of seven metastatic lesions (including three cases involving normal-sized lymph nodes) and correctly predicted the absence of tumor in six of six lymph node regions, for an overall accuracy of 100% (13/13). The sensitivity of the PET technique for detecting small pulmonary lesions was lower than CT but this could be due to respiratory motion or prior cancer treatment. This initial experience demonstrates the feasibility and clinical potential of FDG-PET for the detection of regional and systemically metastatic malignant melanoma, particularly in extra-pulmonary lesions.