Introduction: Isolated unilateral hypoglossal nerve palsy is an infrequent condition that usually appears in connection to an underlying disease. Rarely, the cause cannot be determined, and there is no symptom remission. Case description: We report two cases of male patients who developed persistent idiopathic isolated unilateral hypoglossal nerve palsy. The younger patient complained of involuntary movements of the tongue, while the older patient developed dysarthria. In both cases, the symptoms lasted for several weeks before the initial clinical examination, and after comprehensive clinical, laboratory, and imaging investigations, no underlying cause was detected. Both patients did not show remission of symptoms on the follow-up examinations done after several months. Discussion: Idiopathic isolated unilateral hypoglossal nerve palsy is an underreported condition, most likely due to the expected reversible nature of the disease. In the case of persistence of symptoms, extensive medical assessment is needed before postulating a diagnosis of persistent idiopathic isolated unilateral hypoglossal nerve palsy. There are no treatment guidelines for this condition, but oral steroids were reported as a treatment option. Therefore, physicians should use a systematic approach to exclude serious underlying pathology or identify a treatable condition.