The occurrence and prognostic implications of perineural spread were examined in 239 patients with mucosal squamous carcinomas of the head and neck. Perineural spread was demonstrated in resections from 64 patients (27%), the majority having primary tumors at one of three sites: buccal cavity, larynx, and pharynx. Perineural spread near nodal metastases was uncommon. There was no evidence that perineural involvement was more commonly associated with large tumors or less differentiated ones. No association was established between perineural spread and coexistent lymph node deposits in the surgical resections. Perineural spread was, however, shown to be a statistically significant prognostic factor for an increased incidence of subsequent locoregional recurrence and for decreased survival.