PU.1 is a member of the Ets family of transcription factors and is required for the development of multiple hematopoietic lineages. It plays a pivotal role in normal myeloid differentiation, and regulates the expression of immunoglobulin and other genes that are important for B-cell development. PU.1 stains B lymphocytes in germinal center and mantle B cells, but not plasma cells. It labels many types of B-cell lymphomas including mantle cell lymphoma, but is not expressed in classical Hodgkin lymphoma (cHL). The lack of transcription factor PU.1 protein expression in cHL, a lymphoproliferative disease of predominantly B-cell origin, likely contributes to the lack of immunoglobulin expression and incomplete B-cell phenotype characteristic of the Reed-Sternberg cells in cHL.