The t(11;14)(q13;q32) between the BCL-1 and immunoglobulin heavy chain gene (IgH) loci in mantle cell lymphoma (MCL) are believed to be mediated by the mechanism of V(D)J recombination similar to the t(14;18) in follicular lymphoma(FL). We have recently shown that the t(14;18) event creates staggered double-strand breaks in the BCL-2 locus, and that the t(14;18) junctions contain templated nucleotide insertions(T-nucleotides; U. Jäger et al., Blood, 95: 3520–3529, 2000). Reasoning that the earlier(pregerminal center) B-cell origin of MCL might be reflected in a different molecular structure of the chromosomal breakpoints, we PCR-amplified diagnostic samples from 93 patients. Thirty-six samples(39%) were positive for the direct(BCL-1/J_H) and 23 for both direct and reciprocal (D_H/BCL-1) junctions. The breaks on chromosome 14 exhibited features of V(D)J-mediated recombination as shown by D_H and J_H coding end processing. However,duplications of BCL-1 sequences in 39% of the 23 patients indicate staggered double-strand breaks in the major translocation cluster region (MTC). This is incompatible with V(D)J recombination and indicates a different mechanism of cleavage. The use of J_H6 in the junctions (39%) was similar to that in the immunoglobulin genes of normal B cells and B-CLL,but considerably less than in FL. Only 2 of 36 samples contained a BCL-1/DJ_H rearrangement, which was indicative of a previous DJ_H rearrangement. Most importantly, 19% of the BCL-1/IgH junctions with inserts of ≥5 nucleotides contained error-prone copies (T-nucleotides)of 8–12 nucleotides originating from the surrounding BCL-1 or IgH regions, a lower rate than in FL. No correlation was found between the addition of T-nucleotides and the rate of somatic mutation in the immunoglobulin genes. We conclude that the t(11;14) and t(14;18) use the same basic mechanism of translocation including V(D)J-mediated recombination, double-strand staggered breaks, and template-dependent, error-prone DNA-synthesis. However, the distinct differences in the utilization of J_H regions suggest that the t(11;14) occurs predominantly during an attempted primary D_H-J_H rearrangement in early B cells, whereas the t(14;18) mostly occurs during secondary rearrangement. This is in agreement with the pregerminal center B-cell origin of MCL.