Immunoglobulin and T cell antigen receptor genes in their germ-line form are organized as discontinuous DNA elements that are joined by recombinations during lymphocyte development. The analysis of immunoglobulin gene structure and arrangement has been of great value in the study of human lymphoid neoplasms. The analysis of rearranged immunoglobulin and T cell receptor genes has been of value in defining the lineage (T or B cell) of neoplasms that were of controversial origin previously, determining the clonality of abnormal lymphocyte proliferations, diagnosing and monitoring the therapy of lymphoid malignancies, determining the state of maturation and the causes for failure of maturation of cells of the B cell series, and providing major insights into the cause of malignant transformation of B and T lymphoid cells. Thus, the application of this molecular genetic approach has great potential for complementing conventional marker analysis, cytogenetics, and histopathology, thus broadening the scientific basis for the classification, diagnosis, and monitoring of the therapy of lymphoid neoplasia.