BACKGROUND: In transsphenoidal endoscopic cranial base surgery, a precise navigational support may be crucial. This is particularly evident when tumors extend to the parasellar region or in recurrent tumors whereas normal anatomy has been altered by previous surgery/radiotherapy. - METHODS: Previous unsatisfactory experiences with various navigation techniques in this type of surgery encouraged us to perform an endoscopic endonasal approach with an O-arm (Medtronic, Inc., Minneapolis, Minnesota, USA) assisted technique for the surgical treatment of 4 patients affected respectively by an orbital tumor and 3 cases of relapse of nonfunctioning pituitary adenoma, 1 of them localized in the infrasellar-clival region. - RESULTS: The system O-arm-StealthStation allows for merging intraoperative bone 3-D acquisition with preoperative computed tomography/magnetic resonance imaging and provides the surgeon with an extremely reliable operative navigational tool. - CONCLUSIONS: This is the first report of an O-armassisted endoscopic surgery for cranial base tumors. Here we report on the feasibility and usefulness of such a new application of the O-arm: technical details, setting of the operating room, advantages, and limits of the method are also described. Our overall impression, considering the limited number of patients, is that use of the O-arm may be successfully extended to selected cases of cranial base tumors operated through an endoscopic endonasal approach.