In the current study, the authors established a novel metastatic model to analyze organ selective metastasis by osteosarcoma, using a murine cell line, Dunn osteosarcoma. The lung, liver, kidney, and spleen were resected from syngeneic donor mice, and a tissue fragment of the respective organs was transplanted subcutaneously into a recipient mouse. Two weeks later, tumor cells were injected intravenously and the formation of metastatic deposits in the ectopic transplants was examined. Ectopic lung transplants had a significantly higher incidence of metastasis than either liver or kidney transplants. When enzymatically dispersed organ cells that were embedded in agar gel were transplanted, intravenous injection of tumor cells also resulted in a higher metastatic rate in lung transplants than in either liver or kidney transplants. Photomicrographs and microangiographs of the transplants showed equivalent revascularization of the different organs. Radiolabeled tumor cells were deposited in equivalent amounts in the ectopic transplants of the different organs after intravenous injection. In addition, in vitro growth of tumor cells was stimulated by medium conditioned with lung tissue in a dose-dependent manner. These results suggest that organ selective metastasis by osteosarcoma is not defined anatomically or hemodynamically, but may be caused by tumor cells responding to possible paracrine factors emanating from the lung.