One of the reasons for the development of hypoglycemia is the synthesis of autoimmune antibodies to insulin or its receptor – insulin autoimmune syndrome (IAS). The largest number of cases of this syndrome is described in the Japanese population. The antibodies to insulin are most often polyclonal immunoglobulins. In monoclonal gammopathy of undetermined significance and multiple myeloma secreted pathological monoclonal immunoglobulin may have an affinity for human insulin, which induces the development of IAS. The prolonged persistence of episodes of hypoglycemia of unknown origin requires the exclusion of the monoclonal nature of secreted antibodies to insulin. Often the presence of pathological secretion for a long time is not recognized due to the absence of other manifestations of the disease. The manifestation of gammopathy is represented by a wide range of symptoms and syndromes requiring the collaboration of doctors of various specialties. This review summarizes the literature on IAS in patients with monoclonal gammopathy, whose disease debuted from episodes of spontaneous hypoglycemia. When hemoblastosis remission is achieved (when the secretion of the pathological protein is minimal or not determined), the glucose, insulin, and antibodies levels of insulin normalize, and when multiple myeloma recurs, episodes of hypoglycemia resume. The onset of the disease from the IAS can be considered as a new criterion for symptomatic multiple myeloma, dictating the need for the initiation of specific therapy.