Clonality of T- and B-cell lymphoproliferative disorders can be determined by gene rearrangement studies when morphology and surface immunostaining are nondiagnostic. TcR and lg gene rearrangements have been demonstrated in many different hematologic disorders and TcR gene rearrangement has been particularly useful in the diagnosis of patients with CD8 large granular lymphocyte leukemias. TcR gene rearrangement may also be useful to distinguish Hodgkin's disease from T-cell non-Hodgkin's lymphoma. Gene rearrangement is usually performed by Southern analysis, and it is beneficial to run multiple enzyme-probe combinations to maximize the detection of clonal rearrangements. More recently, several laboratories have begun to use polymerase chain reaction (PCR) for gene rearrangement analysis. PCR offers an improved turnaround time, eliminates partial digestion artifacts, and allows for the use of paraffin embedded material. In addition to rearrangements of the TcR and lg genes, analysis of alterations in other genes such as bcl-1, bcl-2, bcl-6, and c-myc are also useful as clonal markers and aid in the classification of lymphomas.