The aim of the study is to assess the feasibility of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of multiple myeloma and compare to skeletal survey (SS), using bone marrow biopsy and whole-body magnetic resonance imaging (WBMRI; where available) as gold standard. Patients referred over an 18-month period for investigation of suspected multiple myeloma or restaging of myeloma were randomized to undergo one of two WBLDCT protocols using high kVp, low mAs technique (140 kVp, 14 mAs; or 140 kVp, 25 mAs). Recent WBMRI scans were reviewed in 23 cases. Each imaging modality was assessed by two radiologists in consensus and scored from 0-3 (0 = normal, 1 = 1-4 lesions, 2 = 5-20 lesions, 3 a parts per thousand yenaEuro parts per thousand 20 lesions/diffuse disease) in ten anatomical areas. Overall stage of disease, image quality score, and the degree of confidence of diagnosis were recorded. Diagnostic accuracy of skeletal survey and WBLDCT were determined using a gold standard of bone marrow biopsy and distribution of disease was compared to WBMRI. Thirty-nine patients were evaluated. WBLDCT identified more osteolytic lesions than skeletal survey with a greater degree of diagnostic confidence and led to restaging in 18 instances (16 upstaged, two downstaged). In those with recent WBMRI, distribution of disease on WBLDCT showed superior correlation with WBMRI when compared with SS. Overall reader impression of stage on WBLDCT showed significant correlation with WBMRI (kappa = 0.454, p < 0.05). WBLDCT provided complementary information to WBMRI in nine patients with normal marrow signal following treatment response, but which were shown to have diffuse residual cortical abnormalities on CT. WBLDCT at effective doses lower than previously reported, is superior to SS at detecting osteolytic lesions and at determining overall stage of multiple myeloma, and provides complementary information to WBMRI.