Analysis of B-cell-specific transcription factors is useful in understanding of the differentiation-linked phenotype in Hodgkin's as well as in non-Hodgkin's lymphomas. We analyzed the expression profiling of transcription factors Pax-5, Oct-1, Oct-2, BOB.1, and PU.1 in 109 cases, including non-Hodgkin's lymphomas of B- and T-lineage, classical Hodgkin's lymphomas, and nodular lymphocyte predominant Hodgkin's lymphomas. Our study revealed that all transcription factors were universally expressed in all cases of nodular lymphocyte predominant Hodgkin's and variably expressed in non-Hodgkin's lymphomas of B-lineage. Cases of classical Hodgkin's lymphoma variably expressed the Pax-5, Oct-1, Oct-2, and BOB.1. However, in contrast to nodular lymphocyte predominant Hodgkin's lymphoma, the transcription factor PU.1 was consistently absent in all cases of classical Hodgkin's lymphoma. Transcription factors Pax-5, BOB.1, and PU.1 were not detectable in cases of anaplastic large cell lymphoma. However, the Oct-1 was detected in all anaplastic large cells lymphoma cases, indicating that expression of this transcription factor was not restricted to B-lineage lymphoid malignancies. Our findings suggest that inclusion of the PU.1 antibody may prove useful in separating classical Hodgkin's lymphomas from nodular lymphocyte predominant Hodgkin's lymphomas in problematic cases.