The goal of this study was to evaluate the feasibility of a minimally invasive approach to the middle cranial fossa using a novel endaural keyhole. The charts of all patients who underwent this novel minimally invasive approach to the middle cranial fossa were retrospectively reviewed. In addition, cadaveric dissection was performed to demonstrate the feasibility of the endaural keyhole to the middle cranial fossa. Six patients (5 female and 1 male; age range 47-77 years) who underwent craniotomy for CSF leak (n = 3), intracerebral hematoma evacuation (n = 2), and tumor resection (n = 1) via the endaural subtemporal approach were identified. There were no approach-related complications noted. Representative imaging from cadaveric dissection is provided with a stepwise discussion of the procedure. The endaural subtemporal keyhole craniotomy provides a novel approach to middle fossa skull base pathology, as well as a minimally invasive approach to intra-axial pathology of the temporal lobe and basal ganglia. Further research is needed to establish the limitations and potential complications of this novel approach.