Genetic events underlying pathogenesis of nodal and extranodal marginal zone lymphoma (MZL) are incompletely understood. We report here a novel t(X;14)(p11.4;q32.33) identified in 4 lymphoma cases: 2 with a mucosa-associated lymphoid tissue (MALT) lymphoma, 1 with a nodal MZL and 1 with gastric diffuse large B-cell lymphoma. In all cases lymphoma evolved from a previous auto-immune disorder. Fluorescence in situ hybridization (FISH) and molecular studies showed that t(X;14) which is mediated by immunoglobulin heavy chain (IGH) locus targets the G-protein coupled receptor 34 (GPR34) gene, hosted by the CASK gene at Xp11.4. Upregulation of GPR34 mRNA and aberrant expression of GPR34 protein has been demonstrated in 3 presented cases by qRT-PCR and immunohistochemistry, respectively. GPR34 belongs to the largest family of cell surface molecules involved in signal transmission that play important roles in many physiological and pathological processes, including tumorigenesis. Although functional consequences of t(X;14) remains unknown our studies suggest that upregulated GPR34 activate neither NF-κB nor ERK.