The development of the tools of recombinant DNA technology has implications for clinical oncology. We briefly describe in this article the use of DNA probes as diagnostic tools for the study of leukemias and other malignancies and for the detection of minimal residual disease. Useful DNA markers can be used to assess successful engraftment in bone marrow transplanted patients and to detect mixed chimerism. Immunoglobulin and T cell receptor gene rearrangements can be analysed to investigate the presence of clonal lymphoid populations with pathologic samples and to determine their B or T cell lineage. Point mutations associated with oncogene activation can be detected by hybridization with allele specific oligonucleotide probes, allowing molecular analysis of certain tumors. The level of sensitivity of the different assays are discussed along with their usefulness in the detection of residual malignant cells after appropriate therapy.