Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy. The overall risk of progression to active multiple myeloma has been estimated up to 20% in the first year from diagnosis (Kyle et al, 2007). An angiogenic switch has been postulated as a pivotal event in the progression from MGUS to smoldering myeloma. Two trials for advanced and refractory MM patients tested this hypothesis using Thalidomide as antiangiogenic agent in association with biphosphonates showing and effect on disease progression (Barlogie et al, 2008).