BACKGROUND: Extranodal marginal zone cell lymphoma (MZCL) of MALT-type share similar features with nodal and splenic MZCL regarding morphology and immunophenotype. At the genetic level, recent cytogenetic studies have shown that t(11;18) is a recurring abnormality in extranodal MALT-type MZCL but has hitherto never been reported in nodal or splenic MZCL. The aim of the present study was to determine the prevalence of t(11;18) in a large series of nodal, splenic and extranodal MALT-type MZCL, using a sensitive real-time RT-PCR method. MATERIALS AND METHODS: Ninety-three MZCL cases were divided on clinical grounds into 61 extranodal MALT-type, 19 splenic and 12 nodal MZCL. One case that presented with a massive splenomegaly but for which also gastro-intestinal localisations were found, was left unclassified. A real-time RT-PCR method for the detection of the API2-MLT fusion resulting from t(11;18) was performed on RNA extracted from frozen tissue sections. RESULTS: The API2-MLT fusion was detected in 12 cases, which were all extranodal MALT-type lymphomas of the stomach, except for one case. The remaining positive case was the unclassified case, for which the translocation was detected in the spleen and in hilar lymph node tissue. CONCLUSIONS: While similarities between MZCL from different anatomic sites have lend us to propose that all MZCL have a common normal counterpart, the almost exclusive detection of t(11;18) in gastric MALT-type lymphoma favours its recognition as a separate lymphoma entity. The absence of the translocation in nodal and splenic MZCL challenges the idea of these lymphomas being secondary to MALT-type lymphomas of the gut. The unclassified case illustrates the inadequate approaches available at present to identify and define the various MZCL.