Diffusion-weighted imaging (DWI) is sensitive for the detection of acute ischemic stroke. However, a negative DWI study of the brain does not always exclude a patient from the possibility of acute cerebral ischemia. The authors report 1 case in which the patient presented with a fixed ischemic neurological deficit (National Institute of Health Stroke Scale score = 22) that included global aphasia, right hemiparesis, and a right visual field neglect. The initial DWI of the brain within 27 hours of symptom onset was negative. The deficit persisted, and a repeat magnetic resonance imaging study 7 days later showed a large area of restricted diffusion involving the gray matter of the entire left middle cerebral artery and anterior cerebral artery distribution, indicating a large area of cortical stroke.