Objective: To describe an isolated unilateral sixth nerve palsy, as a rare neuroophthalmic presentation of nasopharyngeal carcinoma. Methods: We report a 54-year-old female, known case of nasopharyngeal carcinoma who was treated with chemo-radiotherapy, and presented with isolated right sixth nerve palsy. Magnetic resonance imaging (MRI) indicated extension of tumor to intracranial fossa with clival involvement. Results: The patient was referred to an otolaryngologist for further evaluation and necessary intervention due to invasion of the cancer to intracranial fossa with involvement of right abducens nerve. Conclusions: Although, isolated sixth nerve palsies in adults over the age of 50 are usually ischemic; but in enduring cases, neoplastic processes should be considered.