Chronic myelocytic leukemia (CML) may display a lymphoproliferative phase (lymphoid blast crisis) that is generally of B cell phenotype. Since lymphoproliferative disorders may occur following bone marrow transplantation (BMT), it may be difficult to distinguish posttransplant relapse of CML lymphoid blast crisis cells from de novo lymphoproliferation. Lymphoid blast crisis from a patient with CML displayed immunoglobulin heavy chain gene (Cμ) rearrangement before BMT. Following BMT the patient developed a lymphoproliferative disorder involving multiple organs. Clonal rearrangement of Cμ was demonstrated in several involved tissues. The rearranged Cμ restriction fragment was distinct from that displayed before BMT. Additionally, rearrangement of the breakpoint cluster region (bcr) was demonstrated in the pretransplant blast crisis sample, but not in the posttransplant lymphoproliferation samples, thus confirming that these lymphoproliferative disorders were distinct. Molecular genetic techniques offer powerful diagnostic tools for monitoring the course of patients with CML undergoing BMT.