Perineural tumor spread (PNS) of head and neck malignancies is a well-known form of metastatic disease in which a lesion can migrate away from the primary site along the endoneurium or perineurium. This pattern of spread may create a poor prognosis and require aggressive treatment when curable. Although representative histologies are squamous cell carcinoma and adenoid cystic carcinoma, other malignancies such as malignant lymphoma and sarcoma also can show such a specific pattern of extent. PNS can be insidious, often delaying diagnosis. Knowledge of anatomy of the nerves is crucial in the imaging diagnosis of PNS, to detect early curable disease. The facial nerve and the maxillary and mandibular divisions of the trigeminal nerve are most commonly affected. General clinical issues and the diagnostic imaging of PNS along these nerves are discussed in the current article.