From the Istituto di Ematologia e Oncologia Medica "L. e A. Seràgnoli", Università di Bologna, Italia (EZ, PTo, PTa, DC, GP, MC, AB, MB, MC); Istituto di Medicina Nucleare, Policlinico S. Orsola-Malpighi, Bologna, Italia (CN, PC, SF);Clinica Ematologica, Dip. di Ricerca Clinica e Morfologica, Università di Udine, Italia (FP, SB, RF); Istituto di Medicina Nucleare, Ospedale S. Maria della Misericordia, Udine, Italia (EE, OG); Istituto di Radiologia, Policlinico S. Orsola-Malpighi, Bologna, Italia (ES) Correspondence: Michele Cavo, M.D., Istituto di Ematologia ed Oncologia Medica "Seràgnoli", Università degli Studi di Bologna, Policlinico S. Orsola-Malpighi, Via Massarenti, 9 40138 Bologna, Italy. E-mail: mcavo{at}med.unibo.it Background and Objectives: Bone lesions in multiple myeloma (MM) have been traditionally detected by whole body X-ray (WBXR) survey although magnetic resonance imaging (MRI) has become the gold standard for detecting MM involvement of the spine and pelvis. The aim of this study was to compare a new technique, positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) integrated with computed tomography (18F-FDG PET-CT), with MRI and WBXR for baseline assessment of bone disease in MM. Design and Methods: We prospectively compared 18F-FDG PET-CT, MRI of the spine-pelvis and WBXR for baseline assessment of bone disease in a series of 46 patients with newly diagnosed MM. In 23 patients who received up front autologous transplantation, we also compared post-treatment PET-CT scans with MR images of the spine and pelvis. Results: Overall, PET-CT was superior to planar radiographs in 46% of patients, including 19% with negative WBXR. In 30% of patients, PET-CT scans of the spine and pelvis failed to show abnormal findings in areas in which MRI revealed an abnormal pattern of bone marrow involvement, more frequently of diffuse type. In contrast, in 35% of patients PET-CT enabled the detection of myelomatous lesions in areas which were out of the field of view of MRI. By combining MRI of the spine-pelvis and 18F-FDG PET-CT, the ability to detect sites of active MM, both medullary and extramedullary, was as high as 92%. Following transplantation, 15 patients had negative PET-CT scans (including 13 with a very good partial response or at least near complete response), but only 8 had normal MRI. Interpretation and Conclusions: MRI of the spine and pelvis still remains the gold standard imaging technique for the detection of bone marrow involvement in MM. 18F-FDG PET-CT provides additional and valuable information for the assessment of myeloma bone disease in areas not covered by MRI. Key words: 18 F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance imaging, whole-body planar radiographs, bone disease, multiple myeloma.