Background <p>Imaging the trigeminal nerve (TN) presents significant challenges due to its extensive pathway from the brainstem nuclei to its peripheral branches, as well as its complex anastomotic network either through its numerous branches or connections with the facial nerve, which often complicates a topographic approach. Various pathologic conditions may affect each segment of the trigeminal nerve, MRI is the preferred imaging technique for evaluating the majority of conditions that involve various segments of the trigeminal nerve. The majority of the literature surrounding the trigeminal nerve although encompasses a variety of perspectives, but it is focusing on trigeminal nerve involvement in perineural spread from locoregional malignancies and neurovascular compression conflicts. This research manuscript is meant to concentrate on the less familiar trigeminal nerve lesions, escalating perineural sheath of segments distal to the porus trigeminus; those encompassing Meckel’s cave and the cavernous sinus, extending to its peripheral branches, while excluding the preganglionic and brainstem segments.</p> Patients and methods <p>The purpose of our current research is that we can report herein our experience in imaging of different trigeminal nerve related masses, starting from distal to porus trigeminus, so we can separate head and neck/skull base from scope of neuro-radiology. Also, we termed them “non-vascular” to exclude vascular loops, cavernous sinus thrombosis and cortico-cavernous fistulas. This <i>retrospective case study</i> aimed to collect patients’ data from the <i>Archives</i> of radiology department, from January 2022 to January 2024 including MRI imaging data and final pathology results, which were extracted from patients primarily referred for imaging from the “oncology,” “neuro-surgery” and “oto-rhino-laryngology” ward. <i>The “Ethics Committee” of our medical institution approved our proposed protocol.</i></p> Results <p>Our study had enrolled 48 cases: 24 men and 24 women, with ages ranging between 12 and 79&#xa0;years, showing a mean of 43&#xa0;years. The predominant pathology was schwannomas (n = 15), followed by inflammatory pseudotumor/ IGg4 disease (<i>n</i> = 11), followed by meningioma (<i>n</i> = 9), followed by metastases (<i>n</i> = 7). The Cavernous sinus (CS) was the prevalent epicenter location of pathologies (<i>n</i> = 34; 70% of cases), followed by Meckel’s cave (MC), and Masticator space (MS) and PPF-pterygo-palatine fossa (<i>n</i> = 3 for each), followed by orbit and orbital apex (sites of V1).</p> Conclusions <p>Perineural spread along the TN is not limited to PNTS from locoregional head and neck malignancies and has more wide differential diagnosis, and differential list includes quite less common lesions. These unfamiliar lesions of the TN involve the nerve in a similar perineural pattern and yet imaging features are overlapping with common PNTS from local malignancies, making optimal diagnosis a difficult task without pathology confirmation. However, radiologists should be aware of such uncommon lesions which should be included in differential diagnosis of PNTS.</p>