Diagnosis of leukemia and lymphoma has been made by morphological, cytochemical, and immunophenotypical methods. Recently molecular biological approaches have been introduced to clarify the cellular lineage of the tumor cells and to demonstrate the monoclonality. Southern blot analysis using immunoglobulin (Ig) and T cell receptor (TcR) genes revealed the presence of monoclonal components in some cases of angioimmunoblastic lymphadenopathy (AILD), in which demonstration of monoclonality was difficult by conventional methods. In preB-ALL, many cases had rearranged IgH and TcR genes simultaneously. These "dual genotype" cases were found to be of accidental involvement of TcR gene in the process of making effective IgH gene rearrangements by the precise analysis of rearranged IgH gene structures. The rearranged TcR gene which was detected in initial lymphoblastic lymphoma cells, was observed in relapsed blasts after lineage conversion to myeloid leukemia, which indicates the same clonal origin. Diagnosis and detection of minimal residual disease by the polymerase chain reaction (PCR) are now recognized as sensitive methods. PCR using oligonucleotides common to each VH and JH gene detects the rearranged IgH gene sensitively. PCR using primers located on the translocation boundary, such as bcr and abl in CML, is very useful in the diagnosis and pursuit of the disease course. PCR study also can be applied to the detection of alteration of some particular genes such as tumor suppressor genes.