This prospective study was undertaken to investigate the appearance of multiple myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient management were evaluated. Forty-three patients with known multiple myeloma (n=28) or solitary plasmacytoma (n=15) underwent FDG-PET. The results of routinely performed radiographs and of scans obtained using all available imaging modalities (MRI, CT), as well as the clinical course, were used for verification of detected lesions. Focally increased tracer uptake was observed in 38 of 41 known osteolytic bone lesions (sensitivity 92.7%) in 23 patients. In addition, 71 further bone lesions which were negative on radiographs were detected in 14 patients. Twenty-six (36.6%) of these lesions could be confirmed in ten patients. As a result of FDG-PET imaging, clinical management was influenced in five (14.0%) patients. The positive predictive value for active disease was 100% in patients with focal or mixed focal/diffuse skeletal FDG uptake and 75% in patients with diffuse bone marrow uptake. Depending on the interpretation of the PET scans in patients with diffuse bone marrow uptake, the sensitivity ranged from 83.8% to 91.9% and the specificity from 83.3% to 100%. FDG-PET thus proved highly accurate in detecting multiple myeloma, and revealed a greater extent of disease than routine radiographs in 14 of 23 (60.9%) patients who had osteolytic bone lesions. FDG-PET might contribute to the initial staging of solitary plasmacytoma.