Recombinant DNA technology has provided a wealth of new observations in the study of lymphoma. Progress has been enhanced by the unique rearrangement of immune-specific genes during normal lymphocyte differentiation. Because these gene rearrangements are irreversible and are inherited in all cellular progeny, lymphoid tumors have a monoclonal genomic structure. Molecular analysis of genomic structure is a powerful new method of assessing clonality and lineage to supplement histologic examination in achieving accurate diagnosis and staging of lymphomas. Furthermore, the frequent occurrence of translocations in lymphoid neoplasms provides a second pathway for genomic analysis. In 57 B-cell lymphomas tested by Southern blot and polymerase chain reaction, the authors found evidence of bc12 gene translocation in 100% of follicular small cleaved cell lymphomas, 67% of diffuse small cleaved cell lymphomas, 33% of mixed lymphomas, 25% of diffuse large cell lymphomas, and 25% of small noncleaved lymphomas. They also describe their experience with immunoglobulin heavy chain and T-cell receptor beta chain genomic analysis as well as review the published literature on the utility of molecular genetics in the classification and staging of lymphoma. Future applications of molecular diagnostics in the clinical management of lymphoma patients are assessed.