Headache is one of the most common neurological symptoms reported by patients with thrombotic thrombocytopenic purpura (TTP). Reports of headache characteristics in patients with TTP are rare. We report 2 cases of headache in a setting of TTP and review previous reports. Headache in TTP can have features in common with both migraine and tension-type headache. Although the pathophysiology of headache in TTP is not certain, platelet aggregation and activation may play a key role.