Thrombotic thrombocytopenic purpura (TTP) is a haematological syndrome characterised by a dramatic onset requiring an urgent treatment with plasma exchange (PE). However, the prognosis is still dismal for PE related complications, a rate of failure and remarkable frequencies of relapse. TTP post transplantation is largely described as an outstanding, unusual complication of allogenic transplantation, but it is rarely mentioned after autologous transplantation. We describe a 62-year-old Caucasian patient who presented with TTP, accompanied by renal failure, after an autologous transplantation for multiple myeloma. PE together with hemodialysis was rapidly initiated but without any benefit. Since empirical administration of Rituximab, anti CD20 monoclonal antibody,was reported to be effective, we administered four courses of Rituximab inducing a complete remission of TTP and subsequently of the renal failure. This response to Rituximab in TTP post transplantation is suggestive of a possible implication of B-lymphocytes in the pathogenesis of TTP and it paves the way for an investigational approach in this settings.