Chromosomal translocations juxtaposing different oncogenes to the immunoglobulin (IG) loci are the hallmark of various B-cell lymphomas. Because the tumor cells in nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) are also derived from B cells, we examined whether NLPHL harbors chromosomal translocations that affect IG loci. Fluorescence in situ hybridization was applied to 24 NLPHL cases using probes flanking the IGH, IGK, and IGL loci as well as the BCL6 gene. Fourteen of these cases were additionally analyzed by combined immunofluorescence and fluorescence in situ hybridization. Chromosomal breakpoints in the IGH locus were detected in five NLPHL. All these cases also contained a BCL6 breakpoint. Triple-color interphase cytogenetics demonstrated the presence of an IGH-BCL6 juxtaposition, indicating a t(3;14)(q27;q32) in all five cases. There was no evidence for breakpoints affecting the IGK or IGL loci. Our results show that translocations juxtaposing the BCL6 oncogene next to the IGH locus are recurrent in NLPHL.