BACKGROUND. The authors undertook a prospective evaluation of the clinical value of 2-fluoro [18-1-2·deoxyglucose positron emission tomography (FDG-PET) in the detection and staging of malignant lymphoma compared with computed tomography (CT) and bone marrow biopsy (BMB). METHODS. Fifty-two consecutive patients with untreated malignant lymphoma were evaluated prospectively in a bicenter study. FDG-PET, CT, and BMB were performed for investigating lymph node/extranodal manifestations and bone marrow infiltration. Thirty-three percnt of the discrepant results were verified by biopsy, magnetic resonance imaging, or clinical follow-up (range, 4-24 month). RESULTS. Altogether, 1297 anatomic regions (lymph nodes, organs, and bone marrow) were evaluated. FDG-PET and CT scans were compared by receiver operating characteristic (ROC) curve analysis. The area under the BOC curve were as follows: lymph nodes, 0.996 (PET) and 0.916 (CT); extranodal, 0.999 (PET) and 0.916 (CT); supradiaphragmatic, 0.996 (PET) and 0.905 (CT); and infradiaphragmatic, 0.999 (PET) and 0.952 (CT). In these analyses, FDG·PET was significantly superior to CT (P < 0.05), except in infradiaphragmatic regions, in which the two methods produced equivalent results. In detecting bone marrow infiltration, FDG-PET was superior to CT and was equivalent to BMB. In 4 of 52 patients (8%), FDG-PET led to an upstaging and a change of therapy. CONCLUSIONS. Noninvasive FDG-PET is very accurate in the staging of malignant lymphoma. Compared with standard staging modalities (CT and BMB), PET was significantly superior and led to changes in the therapy regimen for 8% of patients. 889-99