Clonotypic studies identified a population of circulating B-cells in blood samples of patients with myeloma (Bergsagel et al., 1995, Chen and Epstein, 1996), sharing the same clonotypic CDR3 region as is detected in the bone marrow malignant plasma cells (Pilarski et al, 1996, Szczepek et al., 1998). Further studies provided additional insights into the evolution of the myeloma clone supporting a notion of heterogeneity of the population of clonal cells in myeloma (Taylor et al., 2002). The B-cell component of the myeloma clone appeared to be clonogenic in xenografted mice (Pilarski et al., 2000; Reiman et al., 2001). Moreover, clonotypic cells with B-cell phenotype express CD19+/CD20+ antigens and may represent a reservoir of disease that persists after therapy, including high dose chemotherapy (Kiel et al., 1999; Rottenburger et al., 1999; Pilarski et al., 2002).