Background. We presented an unusual case of adenoid cystic carcinoma (ACC) of the breast with multinucleated stromal giant cells (MSGCs). To the best of our knowledge, the occurrence of ACC with MSGCs has not been reported previously. MSGCs should be distinguished from other multinucleated giant cells in breast tumors. The histogenesis of MSGCs still remains obscure. In hope to elucidate the histogenesis of MSGCs, we used a broad range of antibodies. Case report. A 40-year-old woman presented with a palpable lump in the subareolar location of her right breast. Excision of the tumor was performed. At gross pathologic examination the tumor was 20 × 15 × 15 mm in size, redbrown and well circumscribed. The surgical margins were positive for carcinoma and skin-sparing mastectomy with axillary dissection was complited. Eighteen lymph nodes examined were uninvolved. Patohistological examination showed ACC with numerous MSGCs scattered within tumor stroma. Immunohistochemical studies indicated that MSGCs are probably derived from stromal fibroblasts. These cells showed strong reactivity only for vimentin. Staining for histiocytic marker (CD68), as well as for epithelial marker (cytokeratin), myoepithelial markers (S-100, α- smooth muscle actin), vascular marker (CD34), hormonal receptors (ER, PR) and HER2 in MSGCs were negative. Conclusion. The presence of MSGCs should not alter the prognosis of an otherwise typical breast ACC.