Despite the fact that numerous studies have been performed on diffuse large B-cell lymphoma (DLBCL), only few have concerned extranodal lymphomas occurring in the testis. We performed a cytogenetic and molecular study of 17 testicular non-Hodgkin lymphomas, of which 14 were proven primary DLBCL of the testis. Cytogenetic analysis revealed in 8 out of 11 evaluable cases a structural abnormality of the long arm of chromosome 6, with deletion or addition of material of unknown origin, and with breakpoints spanning the region 6q12-6q23. The cytogenetic findings were confirmed by fluorescent in situ hybridization (FISH) with a chromosome 6 painting probe. Using array based-comparative genomic hybridization on 16 evaluable cases, including 5 cases not tested by cytogenetics or FISH, 14 (88%) showed chromosome 6q deletions. We identified two regions of minimal deletion (RMD), at 104-113 Mb (6q16.3-q21) and 137.5-138.8 Mb (6q23.3), respectively. In one case, we observed a 2.7 Mb homozygous deletion ranging from 135.3 to 138.0 Mb that partly overlapped with the RMD at 6q23.3. Our study indicates that 6q deletions play a major pathogenetic role in DLBCL of the testis and that many of these deletions are part of unbalanced translocations. (c) 2006 Wiley-Liss, Inc.