Recently the potential of whole-body positron emission tomography scanning using 18F-fluorodeoxyglucose (FDG PET) has led to renewed interest in the use of functional imaging for the detection of occult metastatic melanoma. This study compared dedicated FDG PET with high-dose gallium-67 imaging incorporating whole-body scanning and comprehensive single-photon emission tomography (SPET) in 122 cases (121 patients) in which the two scans were performed <6 weeks apart. All patients were at high clinical risk of occult metastatic disease and 49 (40%) had abnormality suggestive of metastatic disease by at least one functional imaging technique. Discrepant scan findings were followed up to determine which technique more accurately reflected disease status. There were 23/122 (19%; 95% CI: 12%-26%) cases with discordant scan results in respect of either the presence of melanoma (11 cases) or the extent of disease (12 cases). PET correctly identified more disease than 67Ga SPET in 14 cases (including three incidental primary tumours) and was true negative in three further patients with abnormal 67Ga SPET. There were six patients with true positive 67Ga SPET in whom FDG PET was false negative (one small cutaneous deposit, one residual axillary node rated equivocal on FDG PET due to postoperative changes, one adrenal metastasis inseparable from renal activity on FDG PET and three cases in which sites missed on FDG PET were seen on 67Ga SPET. Thus, FDG PET provided incremental diagnostic information compared with 67Ga SPET in 17/23 patients, while 67Ga SPET provided incremental information compared with PET in 6/23 cases ( P=0.035). Based on Australian Medicare reimbursement levels, the net cost per patient with clinical management benefit of replacing 67Ga SPET with FDG PET was estimated to be less than EUR 1,750. These results suggest that FDG PET provides incremental and clinically important information in around 10% of patients at a low incremental cost which, combined with greater patient convenience and lower radiation dosimetry, make FDG PET the functional imaging technique of choice for evaluation of suspected metastatic melanoma.