Isolated hypoglossal nerve (HN) palsy has been reported in a variety of disorders involving the cervical spine and/or skull base, however, unilateral HN palsy caused by rheumatoid arthritis (RA) has rarely been reported. We report herein an uncommon case of isolated HN palsy secondary to RA cervical spine involvement: pannus formation at the C1–C2 articulation, atlanto-axial subluxation, as well as, erosion of the right occipital condyle, lateral mass and anterior arch of C1. Pulse therapy with methylprednisolone followed by maintenance therapy with prednisone resulted in dramatic improvement. We also present the variety of diagnostic modalities helpful for the diagnosis and follow-up.