The nodular lymphocyte predominance form of Hodgkin's disease (NLPHD) is considered as a B cell derived lymphoproliferative disease. A patient with NLPHD presented with an absolute increase in blood B cells with cytological features of mantle zone cells; these B cells were polyclonal, did not exhibit bcl-2 gene rearrangement, and some of them displayed non-clonal chromosomal aberrations. EB virus genome was not detected by Southern analysis. Thus, this study, taking advantage of the presence of an unusual population of blood atypical B cells, confirms data obtained on lymph nodes where, however, malignant cells may be scarce, indicating that NLPHD is a polyclonal B cell lympho-proliferative disease of mantle zone origin.