Imaging diagnosis and therapy monitoring of multiple myeloma (MM) is challenging due to the combined bone and bone marrow involvement and at the same time often imperative due to possible failure of hematological markers (e.g. non-secretory myeloma). MRI is the most powerful MM-imaging technique for visualization of medullar involvement whereas CT optimally detects myeloma bone-disease (BMD). A new CT post-processing software (bone subtraction-BS) is generating subtraction (difference) maps of baseline and follow-up non-enhanced CT exams highlighting the course of BMD. Hence, the purpose of this study was to assess strengths and limitations of these two imaging modalities for longitudinal disease monitoring.