A 63-year-old male with a prior history of thrombotic thrombocytopenic purpura was admitted with sudden onset of syncope. He denied chest pain. His initial blood chemistries were consistent with acute relapse of thrombotic thrombocytopenic purpura as indicated by microangiopathic hemolytic anemia and thrombocytopenia. The patient had evidence of myocardial injury as indicated by elevation of cardiac enzymes. A 12-lead electrocardiogram demonstrated ST elevation (up to 5 mm) in leads V(2) to V(6). The patient was treated with plasma exchange with fresh frozen plasma in addition to nitroglycerin, metoprolol and prednisone in a tapering dose. After reviewing the literature, we believe that the etiology of myocardial damage remains elusive, but may be secondary to an autoimmune phenomenon resulting in microthrombosis and myocarditis. We were unable to find any documentation about any specific treatment in such patients. Further studies are awaited regarding appropriate treatment of patients with thrombotic thrombocytopenic purpura and acute electrocardiographic changes.