It is not uncommon for sarcomatous transformation of the giant cell tumor (GCT) of the bone to occur after radiation, but rarely does malignant transformation occur spontaneously. A few cases have been documented in detail. We report two additional cases of GCT of the bone spontaneously transforming into osteosarcoma. The first case in a 53-year-old man which is absolutely unique and most interesting in that the dedifferentiation process occurred in his right elbow with 7 years of natural history after diagnosis of a primary benign humeral (GCT) tumor. The right upper extremity was resected due to the development of a large tumor with ulcer and bleeding, and pathologic examination demonstrated several small areas of conventional GCT and mass composed of a mixture of GCT and osteosarcoma, low-grade fibrosarcoma, and MPH like pattern. Chemotherapy was chosen because of multiple metastatic nodules in both of his lungs detected by CT scan. The second case involved a man, who had an aggressive tumor in his left distal femoral end. He underwent AK amputation followed by TKA and low dose radiation, and has reported no symptoms for 5 years. The subsequent CT scan for pneumothorax revealed multiple lung nodules. In addition to conventional and benign GCT area, the resection nodules show a second component of very high-grade osteosarcoma. Chemotherapy, mainly MTX and ADR, was performed. Furthermore, lung tumor resection and chemotherapy were repeated.