Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in order to exclude early bone destruction. Studies evaluating magnetic resonance imaging (MRI) in SMM found an optimal cutoff of two or more focal lesions to be of prognostic significance for fast progression into symptomatic disease and considered this biomarker as a myeloma-defining event (MDE) needing to start therapy with the aim to avoid progression to harmful bone lesions. Moreover, studies assessing positron emission tomography (PET) with computed tomography (CT) using 18F-deoxyglucose (FDG) (FDG-PET/CT) in SMM showed that presence of focal bone lesion without underlying osteolysis is associated with a rapid progression to symptomatic MM. Latest IMWG guidelines recommended to perform WBCT (either CT alone or as part of an FDG-PET/CT protocol) as the first imaging technique at suspected SMM and, if these images are negative or inconclusive, to perform whole-body MRI. The goal of this paper is to clarify the role of different imaging modalities in MGUS and SMM workups.