Background: Different topographic patterns in patients who experience an acute ischemic stroke may be related to specific stroke causes. Objective: To determine if lesion patterns on early diffusion-weighted imaging (DWI) are associated with stroke subtypes determined by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Design: Cross-sectional study. Setting: General community hospital. Patients: We studied 172 consecutive ischemic stroke patients with a symptomatic lesion on DWI performed within 24 hours of stroke onset. Main Outcome Measures: Lesion patterns on DWI were classified into single lesions (corticosubcortical, cortical, subcortical ≥ 15 mm, or subcortical < 15 mm), scattered lesions in one vascular territory (small scattered lesions or confluent with additional lesions), and multiple lesions in multiple vascular territories (in the unilateral anterior circulation, in the posterior circulation, in bilateral anterior circulations, or in anterior and posterior circulations). Results: We found an overall significant relationship between DWI lesion patterns and TOAST stroke subtypes (P>.001). Corticosubcortical single lesions (P=.01), multiple lesions in anterior and posterior circulations (P=.03), and multiple lesions in multiple cerebral circulations (P=.008) were associated with cardioembolism. Multiple lesions in the unilateral anterior circulation (P=.04) and small scattered lesions in one vascular territory (P=.06) were related to large-artery atherosclerosis. Nearly half (11/23) of the patients with a single subcortical lesion that was 15 mm or larger were classified as having cryptogenic strokes (P=.001), although 9 of these patients had a classic lacunar syndrome without cortical hypoperfusion. Conclusions: Early DWI lesion patterns are associated with specific stroke causes. Conventional 15-mm criteria for lacunes, however, may underestimate the diagnosis of small-vessel occlusion with DWI.