Osteosarcoma is a malignant bone tumor which usually occurs in the metaphysis of long bones in adolescents or young adults, but the mechanism of disease occurrence is unknown. To examine alterations in the dominant oncogenes in the osteosarcoma and other bone and soft tissue tumors, DNA extracted from 12 bone tumors, 12 soft part tumors and 2 cells lines was hybridized with c-oncogene (c-myc, c-sis, c-raf-1, c-fos, K-ras2, c-erbB, c-fms, c-fos). DNA extracted from the same samples was examined with Rb cDNA (p0.9R, p3.8R) probes, the retinoblastoma gene (Rb gene) localized at 13q14, to analize whether a recessive mutation is a target in osteosarcoma, and other bone and soft tissue tumors. Amplification of c-myc was observed in 3 cases from 7 osteosarcomas and abnormalities in structure of the Rb gene were found in 4 from 7 osteosarcomas, 2 from 4 MFH, and 1 from 2 Ewing's sarcomas. Both amplification of the c-myc and abnormalities of the Rb gene were observed in 3 osteosarcoma cases. The results indicated that both the Rb gene and c-myc oncogene may be involved in the initiation of osteosarcoma.