Malignancies of the sinonasal region and ventral skull base include a varied group of uncommon tumors that are a challenge to treat. These malignancies, with few exceptions, often present late because of their insidious growth and bland symptomatology. As with malignancies of other sites, the primary goal in surgical management is complete resection with negative margins. This presents a unique surgical challenge in that these lesions lie within a region of densely populated anatomic real estate. This fact reinforces the importance of complete preoperative work-up and a sound anatomic understanding. This article discusses key anatomic regions and their importance from an endonasal perspective.