The term monoclonal gammopathy of clinical significance (MGCS) refers to a group of symptomatic monoclonal gammopathies that do not meet the diagnostic criteria for malignant plasma cell disorders, such as multiple myeloma or Waldenström macroglobulinemia. These symptoms are attributable to the paraneoplastic effects of monoclonal immunoglobulins that occur through diverse mechanisms. The presence of symptoms distinguishes MGCS from monoclonal gammopathy of undetermined significance, which lacks significant symptomatic presentation. The presentations of MGCS are manifold, adding to the diagnostic challenge. Clinical suspicion is key for accurate and timely diagnosis. Radiologic imaging can provide pivotal information to guide the diagnosis. In this review, we discuss MGCS from a radiology perspective and highlight pertinent imaging features associated with the disorders.