Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a rescue treatment in multiple sclerosis (MS) patients not responding to first- or second-line therapies. To date, most of the treated cases had a secondary progressive disease course. However, patients with high inflammatory activity, but no secondary progression of the disease, could be candidates to take greater advantage of AHSCT. In this paper, we report two cases with very active, relapsing-remitting (RR) MS, who underwent AHSCT, and obtained a dramatic resolution to disease activity.