- BACKGROUND AND IMPORTANCE: Hypertrophic interstitial neuropathy (HIN) is an uncommon, non-neoplastic lesion typically affecting peripheral nerves. Cranial nerve (CN) involvement is exceedingly rare. We present a case of isolated trigeminal nerve HIN manifesting with V3 distribution neuralgia. CLINICAL PRESENTATION: A 50-yr-old male presented with left sided trigeminal neuralgia refractory to medical management. The patient underwent retromastoid craniectomy for possible microvascular decompression. Intra-operatively, the trigeminal nerve appeared to be focally enlarged with a sausage-like configuration. We selectively resected 1 fascicle which was predominantly involved. Histopathological examination revealed onion bulb formations composed of Schwann cells around centrally placed axons. A diagnosis of HIN was made. Postoperatively, the patient experienced complete resolution of symptoms. CONCLUSION: This is the third case of isolated trigeminal nerve HIN in the literature. We performed a selective resection in a patient presenting with trigeminal neuralgia, resulting in complete resolution of symptoms. It is reported here with intraoperative microscope images, along with a review and analysis of this topic as it related to CN.