...37-year-old IgG-kappa MM patient presenting with progressive, multi-drug refractory EMD….Initial myeloma treatment for the patient occurred over multiple years and included the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, the proteasome inhibitor bortezomib, cortiosteroids, radiation, one autologous and two allogeneic transplantations. She experienced extramedullary relapse...a Q99* truncating mutation as well as a R283K point mutation were observed in CRBN, that we recently demonstrated as essential for the anti-MM action of IMiDs...this is the first description of CRBN mutations in a primary myeloma sample and furthermore of a “triple negative” MM patient possessing mutations probably contributing to resistance to all three major drug classes utilized in MM therapy.