Mantle cell lymphoma (MCL) is a lymphoproliferative disorder with distinct pathologic and clinical features. Genetically, the vast majority of MCLs carry the t (11; 14)(q13; q32). This characteristic chromosomal abnormality leads to deregulation of the CCND1 gene encoding cyclin D1 at 11q13 through juxtaposition with the immunoglobulin heavy chain (IGH) locus at 14q32. By gene expression profiling, 6 cases of MCL that lacked cyclin D1 mRNA expression but had a gene expression signature typical of MCL have recently been described. 1 These cyclin D1–negative MCLs exhibited the characteristic morphologic, immunohistochemical, and clinical features of cyclin D1–positive MCL. In line with the lack of cyclin D1 mRNA expression, cyclin D1 protein was absent in these cases. Moreover, the cases did not have the t (11; 14) by fluorescence in situ hybridization (FISH) analysis. Interestingly, all 6 cyclin D1–negative MCLs expressed either cyclin D2 or D3, suggesting that these cyclins can substitute functionally for cyclin D1 in MCL. 1 Nevertheless, chromosomal aberrations affecting the CCND2 or CCND3gene loci were not detectable in these cases by interphase FISH. Herein, we present 2 cases of cyclin D1–negative MCL in which cyclin D2 protein expression was associated with a chromosomal translocation juxtaposing the CCND2 gene at chromosomal band 12p13 next to the IGK locus at 2p12. The lymphomas occurred in a 33-year-old woman and a 70-year-old man. Both were diagnosed with stage IV disease with bone marrow involvement. Diagnostic lymph node biopsies showed the typical morphology of MCL with a nodular and diffuse growth pattern (Figure 1A, D). Both lymphomas displayed the immunophenotype typical for MCL (CD5, CD20, CD10, and CD23), except for lack of cyclin D1 expression. Absence of the t (11; 14) or variant CCND1 breaks was proven in both cases by FISH using commercially available probes (LSI IGH/CCND1, LSI CCND1 BAP; Vysis, Downers Grove, IL). Conventional cytogenetic R-banding analysis in the first case revealed the tumor cells to have the karyotype 48, XX, t (2; 12)(p12; p13), 3, 21 [11](Figure 1B). Subsequent FISH using recently described probes1, 2 showed that the t (2; 12) caused breaks in the IGK and CCND2 loci, resulting in IGK-CCND2 fusion (Figure 1C insert). In the second case, metaphase analysis was not possible due to lack of suitable material. Nevertheless, interphase FISH showed breakpoints in the CCND2 and IGK loci, as well as IGK-CCND2 fusion (Figure 1E). Immunohistochemical analyses revealed strong nuclear expression of cyclin D2 protein in the majority of the tumor cells in both cases (Figure 1C, F). According to FISH analysis, there was no evidence for breaks affecting the CCND3, CCNE1, or CCNE2 loci in these cases. Cyclin D1, D3, and E expression was only detectable in a few scattered cells, suggesting expression in a minority of tumor cells or bystander cells in both cases (data not shown). Our findings indicate that cyclin D2–positive MCL can arise through juxtaposition of the CCND2 and IGK loci. Remarkably, search of the Mitelman Database of Chromosome Aberrations in