Gliosarcoma is a rare tumor of the central nervous system, consisting of gliomatous and sarcomatous elements. We present an unusual case of gliosarcoma which demonstrated a variation in phenotype over a six month period, changing from a gliosarcoma with osteosarcomatous differentiation, to a gliosarcoma with no osteosarcomatous component. The initial histological diagnosis was glioblastoma multiforme. Fifteen months later the tumor had transformed into a gliosarcoma demonstrating osteosarcomatous differentiation, with the majority of the tumor consisting of osteoid matrix. Further samples taken six months later revealed gliosarcoma with almost no osteosarcomatous component. It is recognized that glioblastoma can undergo a change in phenotype, transforming into a gliosarcoma. This case demonstrates that ongoing changes in phenotype can occur, especially when the tumor has been treated with chemotherapy and radiotherapy. An understanding of the pathological progression of gliosarcoma will become increasingly important as novel treatments for gliosarcoma and glioblastoma become available.