Perineural spread (PNS) refers to the extent of tumor cells or other nonneoplastic lesions along the tissues of the nerve sheath, its overall incidence ranges from 2.5% to 5%. PNS is more frequently associated with carcinoma arising from minor or major salivary glands (more often adenoid cystic carcinoma), mucosal or cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, lymphoma, and sarcoma. Although PNS was previously associated with worsening prognosis, increasing evidence shows that cure is possible. Therefore, radiologists must be aware of the relevant cranial nerve anatomy and thoroughly scrutinize not only the nerves close to the primary tumor site but also the whole neural pathways that can be accessed by PNS. Equally critical is knowledge of the radiologic appearance of perineural tumor extension and the best imaging strategies to detect PNS.