A lymphoma patient in remission that develops a second lymphoma is frequently assumed to have had a relapse of the original lymphoma. However, the second lymphoma may instead be a new lymphoma with a different clonal origin. Comparison of histological characteristics alone is insufficient in many cases to distinguish new lymphomas from recurrent lymphomas. In contrast, clonal origins of B-cell lymphomas can be reliably compared by VDJ rearrangement analysis of B-cell IgH genes. Simultaneous lymphomas have similarly been analyzed by this technique to determine whether or not both tumors share a common clonal origin. Application of VDJ rearrangement analysis in clinical research has been important for characterizing mechanisms of lymphoma development. Furthermore, this technique has the potential to improve treatment of lymphoma patients because management of recurrent lymphomas differs from that of new lymphomas.