This report describes the rare case of a 22-year-old male with persistent idiopathic isolated hypoglossal nerve palsy. Thorough history, examination, and investigation were needed to rule out the many causes of such a presentation. The clinical presentation showed unilateral atrophy and fibrillation of the affected side and mild deviation on protrusion to the affected side. The differential diagnosis included neoplasia, trauma, infection, endocrine, autoimmune, neurologic, and vascular causes. Investigations included magnetic resonance imaging, computerized tomography scan, chest x-ray, cerebrospinal fluid culture, and a range of hematologic tests. These led to a diagnosis of persistent idiopathic isolated hypoglossal nerve palsy.