Perineural spread of head and neck tumor represents extension of the primary tumor along the perineurium. Diagnosis of perineural spread of carcinoma often is delayed unless the clinician maintains a high index of suspicion. It may be insidious, and patients may be asymptomatic for years. Perineural spread of carcinoma has been associated with a poor prognosis; however, it is becoming increasingly realized that cure is possible in some cases, if the full extent of the disease is known and treated. Magnetic resonance imaging (MRI) can detect perineural spread of head and neck carcinoma and define its extent. MRI is the imaging modality of choice to assess perineural disease due to its superior tissue contrast and multiplanar capability. Perineural spread of head and neck carcinomas most commonly involves the trigeminal nerve. Obliteration of the fat within (a) the superior medial orbital (ophthalmic division territory), (b) the periantral fat plane (maxillary division distribution), and (c) the pterygopalatine fossa all are useful indicators of distal perineural disease. A perineural vascular plexus (PNVP) surrounds the trigeminal ganglion and proximal portions of the trigeminal nerve divisions. The trigeminal ganglion and proximal portions of its divisions usually are seen as discrete nonenhancing structures separate from the PNVP. Occasionally, isolated enhancement of the ganglion and the proximal portions of the maxillary and mandibular divisions as they exit the skull base may be seen. This may be an artifact related to head position or may represent avid enhancement of the PNVP. In these situations, evaluating all branches, and the entire course, of the trigeminal nerve for perineural spread can aid in determining whether the apparent enhancement is an isolated normal variant or represents nerve pathology such as perineural spread.