Distinction of lymphocyte predominance Hodgkin's disease (LPHD) from other forms of lymphoma often requires immunohistochemistry (IHC). Most previously published recommended panels include markers to define the large neoplastic cells (for example, CD20, J chain, CD45) as well as the non-neoplastic background cells (CD21, CD45RO, CD57, TiA 1). In the present study we examine the practical use of a double IHC method designed to look simultaneously at two germinal center specific cell types: bcl6+ cells and [bc16+, CD57+] co-positive cells. All 10 nodular LPHD had bcl6+ large cells and numerous CD57+ small background cells, including [bcl6+CD57+] cells in rosettes. One case of LPHD with large cell transformation contained numerous bcl6+ large cells both singly (in areas of typical LPHD) and in sheets (in foci of large cell transformation), many CD57+ small cells but few [bcl6+CD57+] co-positive cells and no rosettes. In none of the five cases of florid progressive transformation of germinal centers were true rosettes seen, although all contained variable numbers of bcl6+ large cells and CD57+ cells. Lymphocyte-rich classic Hodgkin's disease LRCHD cases were notable for bcl6 reactivity in Reed-Sternberg cells in all cases, numerous background small bcl6+ lymphocytes, and rare CD57+ cells. Two phenotypic profiles were associated with the 10 cases of T cell-rich B cell large cell lymphoma (TCRBCL). In the first, group "A," six of six cases had bc16- large cells and few CD57+ small cells, and none had significant numbers of [bcl6+, CD57+] co-positive cells. In the second, group "B," four of four cases had bcl6+ large cells with numerous CD57+ and [bcl6+, CD57+] co-positive cells. These findings not only show that LPHD can be distinguished from its morphologic mimics through identification of specific germinal center cell types, but also identifies a second group of TCRBCL (group "B") whose phenotype suggests it might be an architectural variant of nodular LPHD.