Rationale: Cholesterol granuloma of the breast is a rare disease defined as chronic reactive inflammation of cholesterol crystals and foreign body giant cells. This disease can mimic breast cancer in the clinic as painless palpable hard nodules, and imaging shows irregular hypoechoic nodules with unclear boundaries. Therefore, the uncommon lesions can be easily misdiagnosed as breast cancer. Meanwhile, it can be easily neglected by clinicians because of poor understanding.Patient concerns: In this report, we present a rare case of multiple cholesterol granulomas of the breast, which was analyzed retrospectively and combined with all 11 relevant available studies in the last 50 years. Interventions:The patient had undergone multiple breast imaging inspections for breast nodules and had the local resection of nodules.Diagnoses: The patient was confirmed to have a final diagnosis of benign cholesterol granulomas but was initially considered as breast cancer.Outcomes: The patient did not complain of discomfort after surgery, and ultrasound reexamination 5 months after surgery showed no recurrence.Lessons: By retrospective analysis, dynamic contrast-enhanced magnetic resonance imaging and core needle biopsy can synergistically help clinicians distinguish it from other breast disease. To raise awareness of such a rare disease and reduce related misdiagnoses, we summarize the characteristics of cholesterol granulomas and recommend appropriate novel diagnosis and treatment regimens for patients with cholesterol granulomas.