Immunoglobulin heavy chain gene (IgH) rearrangement was studied in a patient showing the occurrence of classical Hodgkin disease and large B-cell lymphoma (LBCL) in the same lymph node. The VHDHJHregion was amplified by polymerase chain reaction, the template being the DNA extracted from single Hodgkin and Reed-Sternberg and LBCL cells, microdissected on hematoxylin-eosin–stained sections by laser capture. A repeated VH4DH3JH4segment was found in Reed-Sternberg cells, whereas a repeated VH3DH3JH4segment was observed in LBCL cells. Rearranged VHgenes carried somatic mutations in both populations, indicating a common germinal center cell origin. The IgH rearrangement found in clonally related Reed-Sternberg cells differed from the one of LBCL cells in the VHregion but showed the same JHand DHsegments with no variation from the respective germline sequence. The DH–JHjunction is the first immunoglobulin gene segment rearranged in precursor B cells. Because the possibility of secondary Ig gene rearrangement in peripheral lymphoid organs has recently been reported, in the patient described here Reed-Sternberg and LBCL cells might originate from a common precursor in which secondary VHreplacement took place during the germinal center reaction, giving rise to two different clonally related lymphomas.