A case of systemic capillary leak syndrome in a 67-year-old woman is reported. The patient suddenly presented with severe edema and hypotension associated with an increased hematocrit and a decreased level of serum albumin, suggesting capillary hyperpermeability. The patient had IgG kappa monoclonal gammopathy in association with not only a slight increase in plasma cells in the bone marrow but also several punched out lesions in the skull, indicating multiple myeloma. Although most of the cases of systemic capillary leak syndrome reported previously were accompanied by monoclonal gammopathy, this appears to be the first case in which capillary leak syndrome developed in a patient with multiple myeloma.