These studies indicate that monoclonal plasma cells can be detected in the peripheral blood of patients with active myeloma even when they are not detectable by routine WBC differentials performed on Wright-stained blood smears. These cells are usually not present in patients with MGUS and true SMM. They are detected in approximately 60% of patients with new, active MM and over 90% of patients with relapsed or refractory MM. If treatment is effective, they tend to decrease or disappear from the blood. When immunological, molecular, or cytogenetic studies are performed on peripheral blood cells from patients with MM, it must be realized that monoclonal plasma cells may be present and that they can influence the results of these tests. Although monoclonal plasma cells can circulate in the peripheral blood, it is not yet clear whether this cell represents the myeloma stem cell. It is possible that there are precursor cells that do not have plasma cell morphology in the blood or marrow that then differentiate into plasma cells. This question can only be answered by first depleting the plasma cells and then examining the remaining B-cells with appropriate immunological and molecular techniques.