A case of pneumocephalus in a 45-year-old male with undifferentiated rhinopharyngeal carcinoma is described. The patient was initially subjected to radiotherapy and then to transmaxillary resection and a second course of stereotactic radiotherapy for recurrent disease. Lastly, the patient was treated with chemotherapy because of local-regional disease progression. After two cycles of cisplatin, adriablastine and bleomycin, the patient suddenly entered in coma. Cerebral CT scan evidenced the presence of air in the frontal and lateral cornua, in the subarachnoid space of the base cisternae extending to the 7th cervical vertebra. After 8 months of a clinical stationary condition, the patient died. The various treatments used are critically reviewed, and modern therapeutic approaches for the neoplasm and the toxicity involved are discussed. We conclude that in nasopharyngeal carcinoma, for patients who relapse after radiotherapy, successive local-regional therapies (surgery, re-irradiation) should be carefully evaluated to avoid demolishing treatments, which are burdened with severe side effects that might influence the quality of life with only slight improvement of overall survival. Furthermore, the presence of persistant aqueous rhinorrhea in these patients should be carefully evaluated, because it could be an early symptom of a cerebrospinal fluid leak.