Purpose: We describe a patient who presented with unilateral paresthesia after acute isolated infarct of the splenium. Case report: A 74-year-old woman presented with acute onset of right sided numbness and tingling. MR imaging of the brain showed hypointensity on T1-weighted images and on apparent diffusion coefficient maps, and hyperintensity on T2-weighted and on diffusion-weighted images in the splenium, suggestive of acute infarction. MR angiography showed narrowing of left posterior cerebral artery with decreased branches. On detailed high cortical function assessment, she did not have frontal lobe dysfunction, alien hand syndrome, apraxia, optic ataxia, cortical sensation dysfunction, alexia, agraphia, visual field defect, nor color agnosia. Conclusion: Infarcts of the splenium are not common. Splenial lesion may be associated with altered mental status, ataxia, recent seizure, hemispheric disconnection, and dysarthria. The presentation of isolated unilateral paresthesia makes the patient different from those previously described. The paresthesia could be caused by selective lacunar infarcts in the diencephalic and mesencephalic regions or could be caused by the diaschisis in the parietal cortex. Single photon emission CT may be indicated to provide further information of central nervous system dysfunction in splenial lesion.