Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, neurological symptoms, and renal involvement. The relationship of TTP to systemic lupus erythematosus (SLE) has been recognized in the medical literature since 1939. The differential diagnosis is difficult because both diseases have similar clinical features. The mainstay for recognizing TTP in the context of active SLE is the presence of helmet red cells, marked reticulocytosis, and negative direct Coomb's test. We report three female patients with simultaneous presentation of TTP and SLE. We suggest combined treatment with immunosuppressive therapy and plasma exchange using fresh frozen plasma.