We analysed the acquired chromosomal aberrations of 22 marginal zone lymphoma (MZL) patients by various genome-wide cytogenetic techniques, such as G-banding, multicolour fluorescence in situ hybridisation (M-FISH), cross-species colour banding (RxFISH), and comparative genomic hybridisation (CGH), as well as FISH with locus-specific probes. Patients with an abnormal chromosome 3 (n = 11), the most frequently rearranged chromosome, showed a shorter median survival than patients with a normal chromosome 3 (n = 11, 74 months vs. 219 months, P < 0.03). Four of five patients with nodal MZL had chromosome 3 abnormalities and patients with nodal MZL had a shorter median survival than patients in the other morphological subgroups of MZL (P < 0.003). CGH analysis showed only gains of chromosome material, namely of chromosome regions 3p12-25, 3q12-21, 3q23-28, 12q13-15, 12q22-24, 19p13 and 19q13 in two to four cases each (20-40%). In two MZL, the novel unbalanced translocation der(13)t(3;13)(q24;p11) was detected as the sole karyotypic rearrangement, indicating that gain of 3q24-qter could be an important event in the pathogenesis of these lymphomas. Another two cases showed, in addition to other abnormalities, a t(4;14)(p13;q32). Both these lymphomas had involvement of the IGH gene at 14q32, and one of them also of the RHOH/TTF gene at 4p13, which encodes a new member of the RHO protein subfamily.