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Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by deficiency of von Willebrand factor–cleaving protease ADAMTS13. Large von Willebrand multimer formation and intravascular platelet aggregation affecting the arterioles and capillaries can result in death unless early treatment is administered. We report on the case of a child with TTP associated with a human herpes virus type-6 infection occurring during chemotherapy for acute lymphoblastic leukemia who was effectively treated by fresh frozen plasma infusions and antiviral therapy. Although rarely observed in children affected by acute lymphoblastic leukemia, TTP is a potentially fatal illness that should be considered in the differential diagnosis of thrombocytopenia with hemolytic anemia.