A patient presented with acute-onset, painless, unilateral enlargement of the tongue. Steroid treatment for angio-edema was ineffective, and a biopsy of an apparent mass of the tongue base showed normal tissue. Subsequent magnetic resonance imaging showed enlargement, enhancement, asymmetric T2 hyperintensity of the left half of the tongue, and dissection of the left cervical internal carotid artery (ICA) at the skull base. Unilateral enlargement of the tongue due to acute neurogenic denervation may be the sole clinical presentation of a spontaneous arterial dissection at the skull base. The hypoglossal neuropathy resulted from compression by the pseudoaneurysmal ICA dilatation or ischemia from interruption of the vasa nervorum.