Monoclonal gammopathy of undetermined significance is characterized by a serum M-protein level less than 3 g/dL, fewer than 10% plasma cells in the bone marrow, and no or only small amounts of M-protein in the urine; by the absence of lytic lesions, anemia, hypercalcemia, and renal insufficiency; and most importantly, by the stability of the M-protein and by the failure of other abnormalities to develop. Monoclonal gammopathy of undetermined significance is found in approximately 3% of persons older than 70 years and in 1% of those older than 50 years. Approximately one fourth of patients develop MM, AL, WM, or a similar malignant lymphoproliferative disorder during long-term follow-up. In a series of 241 patients at the Mayo Clinic, the actuarial rate of development of serious disease was 16% at 10 years and 40% at 25 years. The median interval from recognition of the M-protein to the diagnosis of MM was 10 years (range, 2-29 years). The plasma cell labeling index and the presence of circulating plasma cells in the peripheral blood suggest active disease. There are no findings at the time of recognition of MGUS that distinguish patients who will remain stable from those in whom a malignant plasma cell proliferative disorder will develop. Therefore, one must perform serial measurements of the M-protein and periodically evaluate the clinical and laboratory features.