Uncommon forms of stromal differentiation are encountered in a minority of fibroadenomas. These include smooth muscle (myoid) metaplasia (51) (Fig. 8.10) and adipose differentiation. Most fibroepithelial tumors with adipose differentiation are phyllodes tumors (52). Giant cells, sometimes with multiple nuclei, are found in the stroma of fibroadenomas (53,54) as well as in phyllodes tumors (54) and other benign breast tumors (55). The nuclei of multinucleated stromal giant cells may be pleomorphic and hyperchromatic (Fig. 8.11). In some tumors these cells to have a florette pattern. These multinucleated cells have ultrastructural features consistent with fibroblasts. In cases studied by the author, the giant cells were reactive for CD68, a histiocytic marker, and only a minority of these cells were immunoreactive for actin or CD34. Multinucleated stromal giant cells are reportedly immunoreactive for p53 and Ki67 (55). Despite their atypical cytologic appearance, the presence of these cells does not influence the clinical course of the lesion. A tumor that has the structural features of a fibroadenoma should not be classified as a phyllodes tumor because the stroma contains multinucleated stromal giant cells. Osteochondroid metaplasia in a fibroadenoma is very uncommon and it almost always occurs in postmenopausal women (56,57).