A lymphoma cell line with a variant type of translocation, t(2;3)(p11;q27), was established from a patient who had received liver transplantation. To elucidate the molecular mechanism of the t(2;3)(p11;q27) chromosomal translocation, we compared the structures of both derivative (der) chromosomal breakpoints with those of their germline predecessors. We noted that the BCL6 gene on chromosome 3 was juxtaposed with the immunoglobulin kappa light chain (Ig kappa) gene on chromosome 2 in a head-to-head configuration. The breakpoint of the BCL6 gene was within a previously reported breakpoint cluster region. The breakpoint on chromosome 2 was within the intron between the leader (L) and variable (V) sequences of one of the V kappa genes, which was fused to the J kappa 3 (J = joining) segment. At chromosomal junctures, a direct repeat duplication of chromosome 3 sequences and a deletion of chromosome 2 sequences were discovered. These results are consistent with a translocation model with illegitimate pairing of staggered double-stranded DNA breaks at 3q27 and 2p11, repair, and ligation to generate der(3) and der(2) chromosomes.