The majority of myeloma cells express CD138, a highly specific surface antigen of terminally differentiated plasma cells, which is absent on highly proliferative normal plasmablast and earlier stages of B-cells (Jego et al., 2001). Based on these observations, it was hypothesized that clonogenic myeloma cells should lack CD138 expression. Using CD138+ and CD138- subsets of cells isolated from myeloma cell lines and from primary myeloma patient samples, Matsui et al. (2004), showed that only a minority of all myeloma cells have CD138- phenotype (<5%). However, only CD138- have clonogenic potential, as demonstrated in colony formation assays in methylcellulose and after transplantation to NOD/SCID mice. Moreover, these cells express B-cell antigens, including CD19 and CD20 and their growth could be inhibited by in vitro treatment with rituximab, an antibody directed against CD20 antigen (Matsui et al., 2004).