A 63 years-old male patient diagnosed with relapsed / refractory multiple myeloma who requires Daratumumab as a part of treatment in the eighth line of management.The flow cytometry showed 63.5% of Plasma Cells with expression of CD38+.Daratumumab + Lenalidomide + Dexamethasone regimen was ordered.After 4 cycles o f treatment, an evaluation o f response was performed a n d documented partial r e s p o n s e .Nevertheless, flow cytometry revealed 4.8% of abnormal Plasma Cells in bone marrow CD38 Negative.Regardless o f the negative expression o f CD38, the optimal r e s p o n s e was continuously evident with daratumumab.A cessation of 6 months was required, but the response to daratumumab was sustainable again after restarting the medication.A 63 years-old male patient was diagnosed with IgA Kappa Multiple myeloma a n d treated i n 2011 with P A D regimen a s a front l i n e .Complete response and posterior consolidation with Autologous stem cell transplant.He relapsed two years after ASCT.Several rescue treatments were given without any response: Rd, CyBorD, Kd, Cyclophosphamide+ Dexamethasone, VRD.Flow Cytometry showed 63.5% of PC with expression of CD38+ (CD38/CD138=63.5% and CD38/CD56 = 63.5%),CD138, CD56, Beta-2 microglobulin, cytoplasmic kappa light chain.CD19 negative, CD45 Negative (Fig 1.).Afterwards, a Daratumumab + Lenalidomide + Dexamethasone regimen was initiated.Partial response was documented.Nevertheless, flow cytometry documented 2,9% of abnormal PC in bone marrow CD38 Negative (CD38neg/ CD138pos = 4.8%, CD38neg/CD56 = 4.8%).CD138+, CD56+, Beta-2 microglobulin, cytoplasmic kappa light chain.CD19 negative, CD45 Negative (Fig 2).Fig 1. Flow cytometry showed 63,5% of myeloma cells (red events)