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Isolated hand weakness is a relatively common clinical presentation. The differential diagnoses include peripheral and central neurological lesions. This is a report of sudden onset, pure hand weakness, without any other neurological signs or symptoms in the setting of a prolonged hospital stay for bilateral diabetic foot ulceration. A cerebral magnetic resonance image identified an “inverted omega sign” along the right precentral gyrus and paracentral lobule, consistent with an area of acute cortical infarction. Patients with acute pure hand weakness, and risk factors for cerebral vascular disease, should be carefully evaluated for a cortical lesion in addition to the routine peripheral neurologic workup.