Protein kinase C (PKC) enzymes play a major role in signal transduction and contribute to the regulation of cellular differentiation and proliferation. However, little is known about subtype-specific intracellular expression of PKC in human malignant lymphoma. To characterize the relationship between expression of PKC and B-cell lymphomas based on the different subspecies, we investigated the expression of four subspecies (alpha, beta II, gamma and delta) in five cases of reactive lymphoid tissues, 77 cases of human B-cell lymphoma and 17 human lymphoma cell lines. In the reactive lymphoid tissues, PKC beta II-positive cells were found in the mantle zones and marginal zones, and centroblasts and centrocytes in the germinal centers showed cytoplasmic staining with strong intensity against PKC delta. The present study is the first report to examine the expression of PKC delta in reactive lymphoid tissues. In interfollicular areas, a small number of T-cells were positive for PKC alpha. Protein kinase C gamma-positive cells were not found in these lymphoid tissues. Eight cases of Burkitt lymphoma (BL) (8/10; 80%) showed the overexpression of PKC alpha (P < 0.01), but other B-cell lymphoma cases except three cases of diffuse large B-cell lymphoma did not express PKC alpha. In addition, six and eight out of nine BL cell lines expressed the protein and mRNA of PKC alpha, respectively. These results indicate that PKC alpha was predominantly expressed on BL in comparison with other types of lymphoma. The expression of PKC gamma was observed in only five cases of BL. The overall survival of PKC gamma-positive BL was significantly better than that of PKC gamma-negative BL (P < 0.05). The expression of PKC gamma seems to be associated with a better prognosis in the limited number of BL cases in the present study.