T-bet, a T-box transcription factor, is expressed in CD4+ T lymphocytes committed to Th1 T-cell development and in a subset of T-cell non-Hodgkin lymphomas. Recent evidence indicates that T-bet also is expressed in B lymphocytes and might participate in immunoglobulin class switching. We examined T-bet expression in 116 cases of B-cell lymphoproliferative disorders by immunostaining and found that T-bet was expressed consistently in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma (14/14 cases) in contrast with precursor T-cell lymphoblastic leukemia/lymphoblastic lymphoma, which is consistently T-bet- (13 cases), as previously reported. T-bet is expressed in memory B cell-derived neoplasms (chronic lymphocytic leukemia, marginal zone lymphoma, hairy cell leukemia; 35/42 cases) but not in cases of mantle cell, follicular, and large cell lymphoma (43 cases). Expression of T-bet in precursor B-cell lymphoblastic leukemia/lymphoblastic lymphoma was confirmed by Western blot analysis. The expression of T-bet in a significant subset of B-cell lymphoproliferative disorders but not in the vast majority of reactive B cells suggests it might have a role in the oncogenesis of T-bet+ B-cell neoplasms. In addition, T-bet should serve as a useful new marker for the diagnosis and subtyping of B-cell lymphoproliferative disorders.