Leukemias and lymphomas are the most extensively characterized forms of neoplasia at the molecular genetic level. Southern blot assays to detect rearrangement of antigen-receptor genes have proven useful in the diagnosis of monoclonality in B- and T-cell neoplasms. This type of assay has clinical utility in that it can detect a small monoclonal population and provide unique information about the clone. Characteristic chromosomal translocations found in various histological types of leukemia and lymphoma can also be detected by Southern blot or by polymerase chain-reaction-based techniques. Detection of point mutations in the ras family of oncogenes may have prognostic importance and permit detection of a monoclonal population in myelodysplastic syndromes and acute leukemias. Viruses may also be involved with leukemia and lymphoma. As assays involving molecular genetics became increasingly important in the evaluation of these neoplasms, greater efforts are needed to improve their technical, laboratory, and clinical aspects.