Although follicular centers are the sites of production of plasma cell precursors, plasmacytic differentiation in follicular center cell (FCC) lymphomas is rarely seen, presumably because of a "block" in differentiation of the large noncleaved FCC. The authors reviewed a large number of these cases to determine the frequency of plasmacytic differentiation in FCC lymphomas. In one hundred ninety-eight, consecutive FCC lymphomas with a follicular pattern from a two-year period, 17 (9%) cases were found in which there were large numbers of plasma cells. Immunoperoxidase studies of paraffin-embedded sections (PIP) for cytoplasmic immunoglobulin showed polytypic marking in ten of these and a monotypic plasma cell population in seven. In this latter group, isotypically identical marking of the plasma cell and FCC populations could be demonstrated in three cases with immunoperoxidase (where the FCCs showed cytoplasmic marking) and in one case (of one tested) with surface typing studies. In addition, three patients had serum paraproteins identical to the plasma cell cytoplasmic immunoglobulins. These findings indicate that a small minority of FCC lymphomas contain sufficient plasma cells to be a diagnostic problem, and that in some of these cases, plasma cells are a differentiated component of the FCC lymphomas.