A case of primary osteosarcoma of the breast in an 83 year-old woman was studied by using a large immunohistochemical panel of antibodies. Tumor cells were stained intensely for vimentin, and focally for alpha-1-antitrypsin. No immunoreactivity was detected for cytokeratin. The absence of an epithelial component excludes a metaplastic carcinoma. The multinucleated giant cells stained strongly for KP-1 antibody, indicating a histiocytic nature. The question is raised whether osteosarcoma of the breast is a malignant tumor de novo, or develops by transformation of a fibroadenoma.