We report a case an adenosquamous carcinoma of the gallbladder that extended to the proximal transverse colon. Metastatic tumor was present in regional lymph nodes and the liver. Microscopically, the tumor was composed of malignant epithelial cells that were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-positive. The adjacent desmoplastic stroma of the primary tumor, as well as the metastasis, contained giant cells that morphologically resembled osteoclasts. Immunohistochemical studies showed that the giant cells were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-negative but weakly alpha 1-antichymotrypsin-positive. While tumors containing osteoclast-like giant cells have been described in the breast, lung, liver, and thyroid, this is the first report of a tumor with this morphology originating in the gallbladder. The presence of the giant cells adjacent to both the primary and metastatic tumor and not at any other location suggests that the tumor cells are producing a substance that induces the formation of the nontumoral giant cells.