The lymphocyte-predominant (LP) type of Hodgkin's lymphoma (HL) is a unique subtype with characteristic tumor cells (lymphocytic and/or histiocytic [L&H] cells) in associated macronodular structures that resemble progressively transformed germinal centers (PTGCs). Immunohistochemical studies have provided strong evidence that L&H cells are of B-cell lineage and recent molecular studies suggested they are transformed centroblasts. A major clonal population is detectable at presentation, with the immunoglobulin heavy-chain gene often showing evidence of continued somatic hypermutation. In developed nations, Epstein-Barr virus (EBV) is infrequently associated with L&H cells and is probably not involved in the pathogenesis of this disease. L&H cells are frequently surrounded by CD3+, CD4+, CD57+, and CD40L- T cells, but the significance of this T-cell rosetting is unclear. LPHL may be associated with concurrent or subsequent large B-cell lymphoma, and there is evidence of a clonal relationship between the two entities. LPHL may also have nodules or large areas that resemble histiocyte-rich B-cell lymphoma (HRBCL). It is likely that at least some cases of HRBCL arise from LPHL. The same may be true of T-cell-rich B-cell lymphoma. Little is known about cytogenetic abnormalities, the cytokine expression profile, and the expression of several functionally important molecules that have been demonstrated in the Reed-Sternberg (RS) cells of classical HL. The challenge for the future is to obtain a more comprehensive molecular profile of L&H cells and their associated T lymphocytes, so as to provide a framework for eventual elucidation of the pathogenesis of this type of HL.