Proper classification of the causative mechanism of stroke is important for optimizing stroke treatment and assessing prognosis. The primary etiology of stroke differs according to race and ethnicity: emboli originating from the heart or extracranial large arteries are common in Western populations, whereas small-vessel occlusion or intracranial atherosclerosis is more prevalent in Asians. Intracranial atherosclerosis frequently leads to stroke by branch-artery occlusion, and the degree of stenosis in these cases is often <50%. Mild intracranial atherosclerotic stenosis may cause distal embolization, if the atherosclerotic plaque is sufficiently vulnerable. Moreover, high-resolution magnetic resonance imaging studies have identified small plaques causing infarction, even in patients with normal-appearing vascular findings. Such cases, which are prevalent in Asia, could not be classified as large-artery atherosclerosis by previous classification systems. Additionally, single subcortical infarctions, which are usually attributed to lipohyalinotic small-vessel disease, can have other causes, including microatheroma of perforators and atherothrombotic lesions at the parental artery. Single subcortical infarctions associated with parental artery disease or those bordering on the main vessel more often have atherosclerotic characteristics than do those associated with lipohyalinosis of the penetrating artery. In countries where intracranial atherosclerosis is common, such atherosclerotic single subcortical infarctions are predicted to be prevalent. These cases, however, could not be appropriately classified in previous systems. Further effort should be devoted to formulate ischemic stroke classification systems that adequately incorporate results of recent studies and reflect the underling pathologic mechanisms, especially in patients with single subcortical infarction and intracranial atherosclerosis.