Phyllodes tumors (PTs) of the breast are uncommon and account for < 1% of all breast tumors. Most patients present with mass lesions; however, there are rare reports of patients presenting with paraneoplastic conditions such as hypoglycemia secondary to insulin-like growth factor II secretion. A 55-year-old woman presented with a rapidly enlarging left breast mass which ulcerated through the skin and invaded the underlying muscle. The serum β-human chorionic gonadotropin (β-hCG) level was found to be 58 mlU/mL preoperatively; this dropped to 2 mlU/mL after surgery. Mastectomy showed a 14.5-cm fibroepithelial neoplasm, the majority of which was composed of a cellular spindle/epithelioid-cell proliferation with the focal presence of elongated epithelial clefts consistent with a PT. In addition to the presence of unequivocal sarcomatous stromal overgrowth and prominent mitotic activity, there were areas of lace-like osteoid production by tumor cells, and a diagnosis of malignant PT with osteosarcomatous foci was rendered. Immunohistochemical studies showed focal β-hCG expression within the epithelioid stroma of the tumor; expression of p63 and cytokeratin was only seen in the epithelial component and there was no expression of placental alkaline phosphatase in either component. Although β-hCG expression/production has been described in many nontrophoblastic tumors (mostly carcinomas of various organs), to our knowledge this is the first case documenting this in a PT of the breast. Whether this intriguing finding represents an isolated association or has more significant implications remains to be determined. © 2009 Wiley Periodicals, Inc.