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We report a case of brain abscess following the percutaneous treatment for trigeminal neuralgia. This procedure envisages the access with a needle into the middle cranial fossa through the oral cavity. Thus, in this case, the bacterial infection can be more likely ascribed to the possible contamination of the needle inside the oral cavity rather than to other frequent and more controllable causes of infection like an imperfect sterilization of surgical instruments or an inadequate antiseptic preparation of both operator’s hands and patient’s skin. The subsequent brain abscess was treated with antibiotic therapy (Vancomycin 2 gr a day and Meropenem 8 g a day for 22 days before the surgical procedure and 30 days after, until complete normalization of laboratory parameters, clinical parameters, and neurological symptoms) and surgical drainage, although the culture of the abscess capsule and the purulent material resulted sterile. In conclusion, the percutaneous therapy for trigeminal neuralgia can be objectively related to risks, even if performed by expert hands. Therefore, it is important that the patient should be advised regarding risks/benefits and/or septic complications of such procedures, even if they occur very seldom. An association of surgery and antibiotic therapy results as effective treatment for this pathologic condition.