Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas is rare. Histologically it mimics the giant cell tumor of the bone and may be associated with a ductal adenocarcinoma. We recently encountered two such cases, both of which were biopsied by EUS-guided FNA. Abundant multinucleated osteoclast-like giant cells and many uniform mononuclear cells were present in case 1 so that the diagnosis was made. In case 2, many mononuclear tumor cells with vacuolated and basophilic cytoplasm were present, and rare osteoclast-like giant cells were seen. A diagnosis of adenocarcinoma was made. In both cases, no conspicuous nuclear pleomorphism was noted in the mononuclear cells or the multinucleated giant cells. The histology of case 2 revealed a pure undifferentiated carcinoma with osteoclast-like giant cells. In addition, a liver biopsy revealed globular amyloidosis. To our knowledge, this is the first report of pancreatic undifferentiated carcinoma with osteoclast-like giant cells sampled by EUS-guided FNA and the first case of hepatic globular amyloidosis associated with this tumor.