B-cell lymphoma 10 (BCL-10) is expressed in the cytoplasm of normal germinal center and marginal zone B-cells and is involved in lymphocyte development and activation. Aberrant nuclear expression of BCL-10 occurs in a subset of extranodal marginal zone B-cell lymphomas (MALT lymphomas), primarily those with the t(1;14)(p22;q32) or t(11;18)(q21;q21). Little is known about BCL-10 expression in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM). We assessed for BCL-10 in 51 bone marrow (BM) specimens involved by LPL/WM using immunohistochemical methods. All patients had monoclonal IgM in serum. Extent of BM involvement was assessed using PAX-5/BSAP and CD20 immunostains and the pattern and percentage of B-cells positive for BCL-10 was determined. The p65 subunit of nuclear factor-kappa B (NF-kappaB), a molecule downstream of BCL-10, was also assessed immunohistochemically. Nuclear BCL-10 staining was present in 28/51 (55%) specimens. BCL-10 expression correlated with greater extent of BM involvement (P=0.001), but did not correlate with serum IgM paraprotein levels, type of immunoglobulin light chain, or clinical variables. Nuclear expression of the p65 subunit of NF-kappaB was detected in 17/50 (34%) specimens, suggesting that NF-kappaB is active in a subset of LPL/WM. p65 NF-kappaB activation did not correlate with nuclear BCL-10 immunostaining. Cytogenetic analysis in 29 cases showed no evidence of the t(1;14) or t(11;18). These results indicate that nuclear BCL-10 expression is common in LPL/WM and does not correlate with MALT lymphoma-associated translocations or p65 NF-kappaB nuclear staining.