Optic nerve injury is a devastating potential complication of endoscopic sinus surgery. Anatomic variations of the posterior ethmoid sinus are certainly contributing factors. In the most well described posterior ethmoid anatomical variant, the sphenoethmoid or Onodi cell, the optic nerve is placed at risk during sinus surgery. Improving preoperative and intraoperative identification of the sphenoethmoid (Onodi) cell could decrease the risk of optic nerve injury. The purpose of this investigation was to assess the reliability of computerized tomography (CT) in detecting the sphenoethmoid (Onodi) cell, and further our understanding of this clinically relevant anatomic variant. A total of 41 sinonasal complexes from 21 human adult cadaveric heads were studied with a standard coronal and axial plane CT, and subsequent endoscopic dissection. The prevalence of the sphenoethmoid (Onodi) cell was determined by CT and endoscopic dissection, as were other anatomic characteristics of the posterior ethmoid anatomy. In our study, CT identified a sphenoethmoid (Onodi) cell in 3/41 (7%) of the sphenoethmoid complexes. However, anatomic dissection identified a sphenoethmoid (Onodi) cell in 16/41 (39%) complexes. Coronal orientation of the anterior sphenoid wall was never associated with a sphenoethmoid (Onodi) cell. Conversely, oblique or horizontal orientations were present in all cases of sphenoethmoid (Onodi) cells. Current CT scanning protocols for the paranasal sinuses did not reliably detect the Onodi cell. Endoscopic dissection indicates that the sphenoethmoid (Onodi) cell is a more frequent anatomic variant than previously appreciated. Awareness of anterior sphenoid wall orientation may assist surgeons in identifying the Onodi cell, thereby reducing the risk of optic nerve trauma.