OBJECTIVE: To evaluate the clinical features, surgical options, and prognosis of middle ear cholesterol granuloma involving the middle cranial fossa. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Medical records of three patients with giant skull base cholesterol granuloma from 2006 to 2017 were retrospectively analyzed. The symptoms, signs, radiological features, treatment options, and prognosis were summarized. RESULTS: All patients underwent radical mastoidectomy and resection of skull base lesions by means of a retroauricular approach. Postoperative pathological diagnosis showed cholesterol granuloma. All patients were followed for more than 1 year. The symptoms were relieved, and there was no recurrence. Postoperative imaging showed that the skull base lesions were cleared and the compressed brain tissue recovered. CONCLUSION: Patients with middle ear cholesterol granuloma involving the middle cranial fossa can be operated on by retroauricular approach. It can reduce the trauma of craniotomy and obtain good curative effect.