Lesions affecting the lateral recess of the sphenoid sinus are rarely discussed in the literature as a separate entity. This region is difficult to visualize and manipulate through the transnasal routes, especially when extensive pneumatization is present. External approaches to this area involve extensive surgery and are associated with significant morbidity. The objectives of this study are to present our experience with the endoscopic transpterygopalatine fossa approach as a method for exposing and manipulating lesions of the lateral recess of the sphenoid and to illustrate the detailed surgical steps of the procedure.