We have cloned and characterized a novel human gene, HGAL (human germinal center-associated lymphoma), which predicts outcome in patients with diffuse large B-cell lymphoma (DLBCL). The HGAL gene comprises 6 exons and encodes a cytoplasmic protein of 178 amino acids that contains an immunoreceptor tyrosine-based activation motif (ITAM). It is highly expressed in germinal center (GC) lymphocytes and GC-derived lymphomas and is homologous to the mouse GC-specific gene M17. Expression of the HGAL gene is specifically induced in B cells by interleukin-4 (IL-4). Patients with DLBCL expressing high levels of HGAL mRNA demonstrate significantly longer overall survival than do patients with low HGAL expression. This association was independent of the clinical international prognostic index. High HGAL mRNA expression should be used as a prognostic factor in DLBCL.