The amplification and rearrangement of five cellular oncogenes (c-myc, c-K-ras, c-fos, c-raf-1, and N-myc) were studied by Southern hybridization in fourteen human bone and soft tissue tumors obtained at surgery. Amplification of c-myc was detected in the two of four osteosarcomas and one of two malignant fibrous histiocytomas. The c-myc genes in these tissues were amplified 4- to 8-fold in comparision with the placenta DNA. One of these osteosarcomas had 16- to 32-fold amplification of c-raf-1 gene without rearrangement. The clinical course of osteosarcoma and malignant fibrous histiocytoma with the amplified c-myc or c-raf-1 gene showed a rapid malignant progress with lung or bone metastasis. There appears to be a correlation between clinical prognosis and oncogene amplification.