The authors investigated ultrastructural cytochemical features of multinucleated and mononuclear stromal cells in giant cell tumor of bone (GCTB), giant cell tumor of tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS). Specimens of each tumor, respectively numbering 4, 4, and 3, were stained for tartrate-resistant acid phosphatase (TRAP) reactions and examined with an electron microscope. In GCTB and GCTTS, multinucleated cells, including some relatively small giant cells, showed TRAP activity and cytoplasmic features characteristic of osteoclasts, and also sometimes abundant rough endoplasmic reticulum and siderosomes. A few giant cells with macrophage-like features and slight TRAP activity were demonstrated in GCCTS and PVNS. In each tumor type, mononuclear cells showing TRAP activity shared cytoplasmic features with osteoclast-like multinucleated giant cells, while some others had macrophage-like features, and still others were poorly differentiated; a few mononuclear cells showed cell-to-cell contact. Ultrastructural similarities of TRAP-positive mononuclear cells in the three tumor types, and those between TRAP-positive multinucleated cells in GCTB and GCTTS, suggest a common cell lineage capable of multinucleated giant cell formation in the 3 tumors, despite differing histogenesis.