We report a case of 43-yr-old Caucasian female with an unusual, cyclin D1 positive marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) type of the mediastinum. To date, only about 30 cases of this entity have been published. They occur mainly in Asian females with a history of coexisting autoimmune disease. To our knowledge, this is the first case of mediastinal MZL with cyclin D1 expression. In the span of 6 yr this patient's tumor recurred three times, was surgically treated, and initially diagnosed as paraganglioma. The diagnosis was based on histopathological examination only. Our final diagnosis of MZL was made by combined evaluation of histopathology (HP), immunohistochemistry (IH), flow cytometry (FCM), fluorescence in situ hybridization (FISH), and molecular biology studies. We found a positive cyclin D1 reaction by IH and cyclin D1 mRNA (CCND1) overexpression by reverse transcription polymerase chain reaction (RT-PCR). Very high cyclin D1 to beta-actin mRNA ratio in this case was comparable with the ratio, characteristic for mantle cell lymphoma (MCL). However, there was no translocation t(11;14) found by FISH and an immunophenotype by IH and FCM was consistent with MZL ruling out MCL diagnosis. In addition, our case differs from other, previously reported thymic MZL lymphoma cases by no autoimmune disease association, Caucasian origin, and the absence of the plasmacytic differentiation on both HP/IH.