Metaplastic mammary carcinoma with osteoclast-like giant cells is a rare neoplasm, and the histogenesis of this tumor remains controversial. A case of metaplastic mammary carcinoma with osteoclast-like giant cells in a 72-year-old woman is reported with p53 mutational analysis. Microscopically, the tumor was composed of a dominant sarcomatous stromal component containing osteoclast-like giant cells and a minor component of intraductal carcinoma. Immunostaining for p53 revealed strong positivity in both intraductal and sarcomatous components, but not in osteoclast-like giant cells. Mutational analysis of the p53 gene disclosed an identical point mutation in both intraductal and sarcomatous components, but not in osteoclast-like giant cells, indicating that both components share the same progenitor cells, and osteoclast-like giant cells represent a reactive infiltrate.