Disease assessment in WM is dependent on the quantification of the IgM monoclonal protein and percent involvement of the bone marrow. There is a need for imaging studies that objectively measure tumor load in these patients. In this study, we sought to examine the role of combined FDG-PET/CT imaging in the detection of tumor load and in the assessment of response to therapy. Thirty-five patients were enrolled on a prospective study using bortezomib and rituximab therapy and were included in this study because they completed a pre-and post-treatment FDG-PET/CT imaging at one facility (12 newly diagnosed and 23 relapsed/refractory). The use of combined FDG-PET/CT imaging showed positive findings in 83% of patients with WM, unlike prior studies using conventional imaging that indicate that only 20% of patients have lymphadenopathy or hepatosplenomegaly. Moreover, 43% of patients had abnormal bone marrow uptake on FDG-PET imaging that can potentially help in the assessment of their tumor load, especially with heterogenous sampling of the bone marrow. There was no statistical correlation between EORTC response criteria for FDG-PET/CT and response by monoclonal protein. This is the first study to examine the role of FDG-PET/CT imaging in WM. Future studies should examine the role of FDG-PET/CT in conjunction with monoclonal protein response in the assessment of progression-free survival in patients with WM. Am. J. Hematol. 86:567-572, 2011. V