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A dilemma presents itself to the otoneurologist and neurosurgeon when determining the least invasive surgical approach to giant cholesterol cysts (GCC) of the petrous apex of the temporal bone. These lesions can be diagnosed with a fair degree of certainty with imaging studies. Transmastoid and subcochlear approaches may be inadequate to access these lesions, and the transcochlear approach results in the sacrifice of hearing. A minimally invasive, combined microscopic and endoscopic sublabial transsphenoid approach to drain and marsupalize these lesions has been chosen by the authors in those cases that are anatomically possible. The purpose of this article is to establish the feasibility of exenterating anterior petrous apex cells by way of this approach, and to better conceptualize the anatomy of the Spheno-Petro-Clival Complex (SPC). Ten Fresh cadaveric “whole head” specimens were dissected with, endoscopic/microscopic control, through midline, sublabial, transseptal, and transsphenoidal routes to the petrous apex. The three-dimensional relationships of the sphenoid sinus, petrous apex, and the clivus were further demonstrated by dissections of the same specimens from the posterior fossa. Sagittal cut sections were also performed. After confirming the feasibility of this approach by dissections, the technique was adopted for performing drainage of GCC of the petrous apex in clinical cases.