Owing to recent advances in medical optical technology, a high-definition (4K) three-dimensional (3D) exoscope has been developed as an alternative tool to using conventional microscopes for microscopic surgery, and its efficacy for neurosurgery has been reported. We report a case who underwent simultaneous surgery aiming for en bloc resection of an anterior skull base malignancy with concurrent exoscopic transcranial and endoscopic endonasal approaches using a 4K 3D exoscope. The patient was a 76-year-old woman who underwent en bloc resection for an anterior skull base olfactory neuroblastoma 13 years ago. After confirming the recurrence of progressive olfactory neuroblastoma, tumor resection was again decided to be performed. As with the first procedure, surgery was performed in an en bloc manner, using both transcranial and endonasal approaches. Exoscope provided enough space above the surgical field to allow us to perform transcranial and endonasal surgeries simultaneously. Moreover, the surgeons could maintain a comfortable posture throughout the procedure, and total tumor removal was successfully achieved without any abnormal event. To our knowledge, this is the first report of the introduction of an exoscope aiming for en bloc resection of an anterior skull base malignancy while performing simultaneous surgery with both transcranial and endonasal approaches. We believe that the more cases are accumulated, the more efficacy of a 4K 3D exoscope will be elucidated.