The Cheiro-Oral (COS) Syndrome is a rare neurologic condition characterized by sensory disturbances involving the peri-oral area and the upper extremity, typically isolated to the hand or fingers. The thalamus contralateral to the symptomatic side is the brain region most commonly involved. Most cases are caused by ischemic or hemorrhagic strokes, although other structural lesions have been implicated. These include tumors, subdural hematomas, aneurysms, and infections. The unusual and seemingly unrelated nature of the symptoms may contribute to misdiagnosis and incomplete workup for potentially serious conditions. We are unable to identify a report of this condition in the emergency medicine literature despite the emergency department being the likely point of presentation for patients with COS. In this report, we describe two patients with COS who presented to our emergency department and review the features of COS as described in published case reports.