A 38-year-old woman presented for evaluation of a firm mass (measuring 20 3 20 mm) in the upper outer quadrant of her left breast. On the basis of the clinical and radiologic findings, we diagnosed a benign breast tumor and scheduled removal by a hand-held vacuum-assisted biopsy device (VABD) under ultrasonographic guidance. Because the first specimen removed from the tumor was white, flaky, and waxy material, we strongly suspected that the lesion was an epidermal cyst. We continued VABD treatment until the tumor was invisible on real-time ultrasonography. Histologic examination demonstrated that the tumor was composed of mature stratified squamous epithelium and laminated layers of keratin, findings consistent with a diagnosis of epidermal cyst. These cysts rarely occur in the breast and are sometimes difficult to distinguish from breast cancer. To our knowledge, this is the first report of an epidermal cyst treated by VABD.