We identified the Human Germinal center-Associated Lymphoma (HGAL) gene in gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL). The expression of the HGAL gene correlated with survival in patients with DLBCL. The HGAL gene is the human homologue of M17, a mouse gene expressed specifically in normal germinal center B cells. Here we generated a monoclonal antibody against the HGAL protein and show that HGAL is expressed in the cytoplasm of GC-lymphocytes and in lymphomas of GC derivation. Among 718 lymphomas tested by immunohistochemistry on tissue microarrays, HGAL staining was found in follicular (103/107), Burkitt (40/40), mediastinal large B (7/8), and in DLBCL (103/151). Nodal and extranodal marginal zone lymphomas lacked HGAL staining. Lymphocyte predominant Hodgkin (12/17) and, surprisingly, classical Hodgkin (78/107) lymphomas were found to be positive. Hierarchical clustering of comparative immunohistologic results in DLBCL demonstrates that the expression of HGAL is similar to two other GC-associated proteins BCL6 and CD10, but different from two markers associated with a non-GC phenotype, MUM1/IRF4 and BCL2. The restricted expression and GC-specificity of HGAL protein suggest that it may have an important role in the diagnosis of specific lymphomas, and, potentially in the identification of subtypes associated with different prognoses.