Cheiro-oral syndrome (COS) is characterized by a sensory disturbance in one hand and the ipsilateral oral corner. It is usually due to a lesion in the parietal cortex, thalamocortical projections or thalamus. Brain stem lesions may rarely produce COS. We present two COS patients with midbrain infarction and pontine hemorrhage, respectively. In our patients, unilateral oculomotor nerve palsy or medial longitudinal fasciculus syndrome concurred with sensory disturbances of cheiro-oral distribution. COS produced by cortical/thalamic lesion is not accompanied with such oculomotor signs. Thus, oculomotor deficits are decisive in differentiating brain stem from cortical or thalamic COS.