Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, radiation hypersensitivity, chromosomal instability and increased incidence of malignancies. In Poland 105 NBS cases showing mutations in the NBS gene (nibrin, NBN), have been diagnosed, approximately 53% of which have developed cancer, mainly (>90%) lymphoid malignancies. This study is based upon the largest reported group of NBS-associated lymphomas. The predominant lymphoma types found in these 14 NBS children were diffuse large B cell lymphoma (DLBCL) and T cell lymphoblastic lymphoma (T-LBL/ALL), all showing monoclonal Ig/TCR rearrangements. The spectrum of NBS lymphomas is completely different from sporadic paediatric lymphomas and lymphomas in other immunodeficient patients. Morphological and molecular analysis of consecutive lymphoproliferations in six NBS patients revealed two cases of true secondary lymphoma. Furthermore, 9/13 NBS patients with lymphomas analysed by split-signal FISH showed breaks in the Ig or TCR loci, several of which likely represent chromosome aberrations. The combined data would fit a model in which an NBN gene defect results in a higher frequency of DNA misrejoining during double-strand break (DSB) repair, thereby contributing to an increased likelihood of lymphoma formation in NBS patients.