New knowledge in cell and molecular biology has begun to expand the understanding of the biology of osteosarcoma and Ewing's sarcoma. Studies on osteosarcomas have revealed abnormalities in the growth-inhibiting retinoblastoma gene, which may release cells from normal growth control. Abnormalities in growth factor production or response tend to inappropriately activate cell growth. Tumor cell DNA content and cytogenetics may affect the diagnosis and prognostic grouping of osteosarcomas. In Ewing's sarcomas, a characteristic translocation between Chromosomes 11 and 22 has been identified; this translocation is also found in malignant neuroepitheliomas. A variety of studies point to both neuroectodermal and mesenchymal origins for Ewing's sarcomas. Applications of new biologic knowledge and technology to clinical problems will lead to significant changes in the diagnosis, and perhaps in the treatment, of these tumors in the coming years. Collaborations between community and referral center physicians and scientists are critical for continued progress.