A retrospective study was performed to characterize 52 new cases of feline epulides between 1995 and 2001, with clinical and pathological results classified according to Head's histopathologic criteria for canine epulides. The incidence of the fibromatous, acanthomatous, ossifying, and giant cell epulis were respectively 57.7% (30/52), 7.7% (4/52), 5.8% (3/52), and 28.8% (15/52). Giant cell epulides presented significant differences in clinical behavior compared with the fibromatous type, including rapid growth (P < .0001), presence of ulcerative changes (P < .01), and rapid recurrence after surgery (P < .01) from which euthanasia was judged necessary in 4 cases. Fifteen giant cell epulides were additionally examined in order to characterize the lesion both histochemically and immunohistochemically and to investigate the origin of the multinucleated giant cells (MGCs). Van Gieson staining showed osteoid and woven bone formation in 11 cases. Both the MGCs and a fraction of the mononuclear cells were positive for vimentin, tartrate-resistant acid phosphatase (TRAP), a commonly accepted marker for osteoclasts, and the polyclonal antibody receptor activator of nuclear factor kappabeta (RANK), a cytokine leading to the differentiation of osteoclast progenitors into mature osteoclasts in presence of its ligand. MGCs were negative for smooth muscle actin, MIB-1, and factor VIII. The giant cell epulis may be a variant of the fibromatous and ossifying epulis in which extensive ulceration and inflammation results in increased osteoclastic activity. The osteoclast-like giant cells are most likely formed from a monocyte/macrophage-like osteoclast precursor that differentiates into osteoclasts under the influence of mononuclear osteoblast-like stromal cells.