: Acute coronary syndrome represents one of the most common causes of admittance to emergency rooms in Western countries. Despite being in the majority of cases the mirror of coronary atherosclerosis, more rare causes could be hidden beyond this presentation, whose identification is often crucial for patients' outcome. We hereby present the case of a 44-year-old woman, with a history of relapsing-remitting multiple sclerosis in treatment with natalizumab, who was admitted to our division for an acute coronary syndrome. At arrival, anaemia and severe thrombocytopenia were observed; thus, no antiplatelet agent was administered. Within a few hours, aphasia occurred. Clinical presentation and the identification of schistocytes at blood smear led to the suspicion of thrombotic thrombocytopenic purpura, which was then confirmed by laboratory analysis. Immediate high-dose steroids and plasma exchange allowed discharging of the patient within a few days without neurological or cardiac sequelae.