We describe a giant cell tumor of the pancreas composed of a mixture of osteoclastic and pleomorphic cell types. This rare tumor had a unique immunohistochemical profile. Both types of tumor giant cells stained for vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, synaptophysin, muscle actin, and neuron-specific enolase, but not for epithelial markers. Electron microscopy showed cells which resembled primitive fibroblasts and osteoclast with no epithelial features. These findings are most consistent with mesenchymal differentiation. The extensive homologies in immunohistochemical staining of both osteoclastic and pleomorphic giant cells in this case indicates that these cells are histogenetically related.