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Introduction: Approximately one third of diffuse large B-cell lymphomas (DLBCL) arises from tissues different from the lymph node. Perceived differences in outcome between extranodal and nodal DLBCL raise the possibility that these subgroups may represent different biological and clinical entities. Methods: Microarray GeneChip technology was used for global gene expression profiles from nodal (n = 19) and extranodal (n = 8) DLBCL, to examine possible differences between these subgroups. Quantitative RT-PCR was employed for validation of microarray data. Differential expression levels of p16 (CDKN2A) were confirmed by means of immunohistochemistry on a tissue microarray comprising more than 200 lymphoma samples. Results: A total of 218, over (124)- and underexpressed (94) genes were found to be differentially expressed in extranodal DLBCL compared with nodal DLBCL, including …