T-box transcription factor TBX21, also known as T-bet, is a member of the T-box family of transcription factors. It has been confirmed that TBX21 is the key lineage-defining transcription factor that directs the development Th1 cells and is directly responsible for the transactivation of the interferon-γ (IFN-γ) gene. TBX21 is expressed in CD4+ T lymphocytes in normal tissues. In lymphoid malignancies, TBX21 has been found in a subset of T-cell lymphomas with Th1 T-cell differentiation, a subset of B-cell or T cells, non-Hodgkin's lymphomas, majority of Hodgkin's lymphomas and precursor B-cell lymphoblastic leukemia/lymphoblastic lymphomas. However, TBX21 is not expressed in diffuse large B-cell lymphoma and most cases of anaplastic large cell lymphoma. TBX21 is a useful new marker for Hodgkin's lymphoma. TBX21 is also helpful in identification of hairy cell leukemia (HCL).