On review of 520 patients with 967 squamous cell carcinomas of the skin of the face treated at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston during a 10 year period, 14 percent of the patients were noted to have perineural extension of tumor. Study of the patients with perineural tumor demonstrated an increased incidence of spindle cell and adenosquamous cell types, an increased incidence of cervical lymphadenopathy and distant metastasis, and significantly reduced survival curves compared with those of patients with squamous cell skin carcinoma without perineural invasion. Tabulation confirmed that the maxillary and mandibular branches of the trigeminal nerve and the facial nerve were most commonly involved. For patients with squamous cell skin carcinomas with perineural invasion, aggressive therapy is recommended, specifically, resection of involved tissues and nerves and appropriate regional lymphadenectomy followed by postoperative radiotherapy. This plan affords the best opportunity for tumor control. The indications for exploration of the middle fossa of the intracranial portion of the trigeminal nerve deserve further study.