An unusual anaplastic thyroid carcinoma with osteoclast-like giant cells is reported in a 72-year-old woman. Monotonous proliferation of variously sized mononuclear tumor cells interspersed with numerous osteoclast-like multinucleated giant cells was dominant. A small area of papillary carcinoma merging with the anaplastic carcinoma was disclosed. Immunohistochemically, tumor cells forming papillary pattern were positive for both thyroglobulin and keratin. Cells and cell clusters positive for keratin were found in anaplastic carcinoma. Electron microscopically, the anaplastic carcinoma cells displayed prominent mitochondria, a rough endoplasmic reticulum, and intermediate cell junctions. The cell clusters formed irregular lumina into which numerous microvilli were extended and which contained colloid-like material. Occasionally incomplete basal laminae were present. Cell clusters showing transitional pictures from cell clusters to multinucleated giant cells and multinucleated giant cells engulfing mononuclear tumor cells were observed by both light and electron microscopy. Findings from this study support the conclusion that anaplastic tumor cells arise in preexisting differentiated thyroid cancer and that associated multinucleated giant cells are formed by the fusion of carcinoma cells.