Properties of bone graft can determine the effectiveness, short and long term success of bone substitution procedure. In this paper, a brief report about advantages and disadvantages of modern bone substitution processes is presented and authors have explicated the opportunity of the usage of gypsum as bone graft. Recently, calcium sulfate dihydrate has been demonstrated as safe biodegradable osteoconductive bone void filler. However, its exact mechanism of action on bone cells and the molecular process of bone substitution is yet unknown. Authors have investigated the effect of gypsum on bone cells using molecular biology methods. Gypsum proved to be an ideal culture surface for proliferation of mice preosteoblastic cells, while polymethilmetacrylate bone cement - generally used in clinical practice as bone substitution material - inhibited cell growth. Gene expression profile of cells has significantly changed on gypsum surface - genes involved in new bone formation have expressed with an increased ratio - and an increased alkaline phosphatase activity has been measured from these cultures. Our results support the use of gypsum as synthetic bone graft and new properties of calcium sulfate dihydrate have been demonstrated due to molecular biological approach.