We previously developed a multivariate model based on the RNA expression of six genes - LMO2, BCL6, FN1, CCND2, SCYA3 and BCL2 - that predicts survival in DLBCL patients. Since LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to study its tissue expression pattern. Immunohistological analysis of over 1200 normal and neoplastic tissues showed that LMO2 protein expression is specific to nuclei of germinal center (GC) B-cells, GC-derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was also expressed in erythroid, myeloid and megakaryocytic precursors and in T- and B-lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature T, NK and plasma cell neoplasms and was absent in non-hematolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of the LMO2 protein was similar to that of other GC-associated proteins (HGAL, BCL6 and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immunohistologic algorithm for predicting survival in patients with DLBCL.