DP-1 is a G1 cell cycle-related protein that forms heterodimers with E2F, a family of transcriptional factors regulating the expression of genes important for G1 to S progression. Although the exact role of DP-1 is not well understood, it has been shown to stabilize DNA binding of E2F proteins. By immunohistochemistry, the authors examined the expression of DP-1 in lymphoid tissues, including 8 cases of reactive follicular hyperplasia and 69 cases of B-cell non-Hodgkin lymphoma. The expression of the cell cycle-related proteins E2F-1 and Ki-67 was also assessed. Scoring was based on the proportion of labeled nuclei (1-10%, 11-25%, 26-50%, and > 50%). In reactive follicular hyperplasia, staining for DP-1, E2F-1, and Ki-67 was largely confined to the germinal centers. All 25 cases of follicular lymphoma, regardless of grade, had a high proportion (> 50%) of DP-1-positive cells but a lower proportion of cells marking for E2F-1 and Ki-67 (P < 0.001). The diffuse large B-cell lymphomas (n = 24) had high DP-1 and Ki-67 scores but low E2F-1 scores (P < 0.001). Small lymphocytic (n = 10), marginal zone (n = 3), and mantle cell lymphomas (n = 5) contained relatively low proportions of cells labeled for all three markers. Precursor B-cell lymphoblastic lymphoma (n = 2) displayed high proportions of cells positive for DP-1, Ki-67, and E2F-1 (> 50% in both cases). Except in follicular center cell lesions, DP-1 expression generally correlated with that of Ki-67. However, the expression of DP-1 was discordant with that of E2F-1 in benign and malignant follicular center cells, suggesting that DP-1 may have functions other than facilitating E2F-1-dependent gene regulation and cell cycle progression in these neoplasms.