Investigation in cellular and molecular genetics has yielded a wealth of new information regarding the role of genetic alterations in the etiology of childhood cancer. The recent advancement of molecular biologic techniques has allowed researchers to bridge the gap from the description of chromosomal aberrations in tumor cells to the current identification of oncogenes and tumor suppressor genes involved in malignant transformation. This article reviews the advances in molecular genetics of childhood cancer, briefly outlines the history, and details the current knowledge of the use of cytogenetics, oncogenes, and other tools in the diagnosis, management, and further understanding of pediatric malignancies.