Previously, a computer-based navigation system has not been used routinely for en-bloc resection of sacral tumors. In order to improve the accuracy of tumor resection, O-arm navigation was used to join anterior and posterior osteotomies during an en-bloc resection of a sacral Ewing's sarcoma. This case study describes the technique for en-bloc resection of a sacral Ewing's sarcoma guided by O-arm computer navigation and intraoperative neurophysiological monitoring (IONM). An 18-year-old male presented with weakness in his left lower extremity. MRI of the patient's spine showed a sacral mass causing compression of left S1 and S2 roots. A surgical resection was planned with anterior and posterior approaches. An O-arm computer navigation system was used to assist in meeting anterior osteotomy cuts with the posterior cuts to ensure complete resection of the sacral tumor with a safe margin. Computer-assisted navigation was used along with IONM during this procedure to help guide the surgical team in an adequate tumor resection. There were no complications related to the use of the O-arm or the navigation system. Computer navigation guidance is both useful and safe in sacral tumor resections. It enhanced the accuracy of the en-bloc removal of a sacral tumor with safe margins while protecting neural function and minimizing recurrence.