Marginal zone B‐cell lymphoma (MZBCL) represents a distinct subtype of B‐cell non‐Hodgkin's lymphoma (NHL) which has been recently recognized and defined as a disease entity. Cytogenetically, these lymphomas reveal a high prevalence of trisomy 3, and recent data obtained by comparative genomic hybridization indicate that the chromosomal regions 3q21‐23 and 3q25‐29 might be of particular pathogenetic significance. We identified structural chromosomal abnormalities involving the region 3q27 and rearrangements of the BCL6 proto‐oncogene in three out of 34 (9%) well‐defined cases of extranodal, nodal and splenic MZBCL using cytogenetic analysis, Southern blot, and fluorescence in situ hybridization (FISH). All three cases were characterized by a t(3;14)(q27;q32). Two of them showed additional chromosomal abnormalities including trisomy 3, which was found in one case. The patients displayed extranodal disease and did not demonstrate any striking clinical and histological differences when compared with MZBCL lacking BCL6 rearrangement. The present study for the first time demonstrates the occurrence of t(3;14)/BCL6 gene rearrangement in MZBCL, thus suggesting a role of the BCL6 proto‐oncogene in the pathogenesis of MZBCL.