Deletions of chromosome 14 recurrently observed in B-cell malignancies are particularly frequent in chronic lymphocytic leukemia (CLL), multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia.1 To characterize these aberrations, we initially mapped the deletions in 23 leukemia/lymphoma cases using a tiling path chromosome 14-array CGH (aCGH) platform (resolution of approximately 42 kb) comprising 838 bacterial artificial chromosome/P1 artificial chromosome (BAC/PAC) clones from the Chori 32K set (www.ensembl.org). Del(14)(q) have been successfully mapped in all 23 cases (Figure 1a) and subdivided into two main categories: (1) involving or (2) not involving 14q32.33. This latter category grouped eight cases with interstitial deletions ranging in size from 17 to 70 Mb and distributed along chromosome 14 (q13 ter) and one case with three dispersed deletions of 1.5, 7.5 and 2.5 Mb. The first category of del(14)(q) comprised 14 cases showing the common distal breakpoint mapped in the 105.26–105.41 Mb region harboring the IGH genes cluster. The size of the deleted region varied in six cases; their proximal breakpoints were bordered by RP11-164H3/95.19 Mb, CTD-2053J06/83.56 Mb, RP11-340F04/74.66 Mb, RP11-350H11/67.94 Mb, RP11-769O09/66 Mb and RP11-520H13/65 Mb. Particularly intriguing was the finding of exactly the same del(14)(q24.1q32.33) covering the region of approximately 36 Mb in eight cases (Figure 1b). The proximal border of this deletion was consistently flanked by RP11-35D12 (68.24 Mb)( 2) and RP11-720I19 (68.45 Mb)( 1), and the distal breakpoint was bordered by RP11-448N05 (105.26 Mb)( 1) and RP11-284A08 (105.43 Mb)( 2). Given that these terminal BACs are assigned to IGCH and IGVH, respectively, aCGH results were additionally validated by fluorescence in situ hybridization (FISH) with the LSI-IGH break-apart probe. As expected, all eight analyzed cases (as well as the remaining six cases with nonrecurrent IGH-involving deletions) showed a one-fusion one-green signal pattern due to loss of the 3'IGH flanking sequences (red signal). The proximal breakpoint of the del(14)(q24.1q32.33) validated with RP11-35D12 and RP11-720I19 showed lost or diminished signal from the latter clone (Figure 1b) and thereby pointed to a breakpoint in the region covered by the overlapping extremities of these BAC clones. The only gene located in this region was ZFP36L1. For FISH detection of the del(14)(q24.1q32.33) in other B-cell non-Hodgkin's lymphoma (B-NHL), a dual-color break-apart assay for the 14q24.1 breakpoint (RP11-35D12-SO/RP11-720I19-SG) and LSI-IGH were applied. The screening of 58 B-NHL cases with cytogenetic and/or FISH evidence of del(14)(q) led to identification of 13 additional cases with del(14)(q24.1q32.33), including one with the deletion masked by t(14;22)(q32;q11)/IGH-IGL (case 7). Additional FISH screening of 60 random CLL cases, seven MM cell lines, including four (RPMI-8226, L-363, OPM-1 and LP-1) with a previously described del(14),2 and 20 various B-NHL cases with structural aberrations of 14q21–q24, failed to identify ZFP36L1 and/or IGH rearrangements, indicating that these deletions are rare molecular events.