In mantle cell lymphoma (MCL), in addition to the characteristic t(11;14)(q13;q32), rearrangements on the 3' side of the cyclin D1 gene have been described. In a series of 32 MCL we found three cases with 3'-rearrangements by Southern blot analysis with a probe representing the 3' untranslated region of the cyclin D1 gene. All three were characterized by the absence of the 4.5 kb transcript, and instead, two cases showed overexpression of the 1.7 kb and a third case (MCLp14) an aberrant 2.5 kb transcript. At the genomic level, fine mapping experiments showed in the 3' untranslated region a 2 kb deletion in MCLp14 and a breakpoint in the other two cases. Fiber FISH analysis showed that in all three cases the 3' aberration co-exists with a regular t(11;14) breakpoint 5' of cyclin D1 on a single allele. Fiber FISH analysis of 16 additional MCL revealed two other such cases with breakpoints 5' and 3' of cyclin D1. These mono-allelic aberrations affecting the cyclin D1 gene suggest that the t(11;14) as a first step switches on transcription, and then sequences in the untranslated region of cyclin D1 are affected to stabilize the message.