Extracapsular spread of squamous cell carcinoma in cervical lymph nodes is associated with approximately 50% decrease in survival and a twofold increase in regional recurrence. This study examines the hypothesis that increased regional recurrence may be, in part, due to unrecognized microscopic perineural invasion of the nerve rootlets of the cervical plexus. Thirty patients with head and neck squamous cell carcinoma with clinically N+ necks undergoing radical neck dissection were prospectively studied. Neck dissection specimens were evaluated for extracapsular spread, and the cervical plexus rootlets were histologically examined for perineural invasion. The incidence of extracapsular spread was 83% (25 of 30 patients). Only one (4%) of 25 had involvement of the cervical plexus, and this patient had gross as well as microscopic cervical plexus invasion. Microscopic perineural spread of squamous cell carcinoma in the cervical plexus occurs infrequently when extracapsular spread is present. Routine histologic evaluation of cervical rootlets for margins is warranted only when gross tumor is in close proximity to the cervical plexus.