Sox11 is a transcription factor involved in embryonic neurogenesis and tissue remodeling. Its role in lymphopoiesis is presently unknown. Recent studies have shown the nuclear expression of sox11 in mantle cell lymphoma, which raises the question about its possible association with t(11;14)(q13;q32), the genetic hallmark of mantle cell lymphoma leading to the overexpression of cyclin D1. In this study, we examined sox11 expression in 211 cases of B-cell neoplasms by immunohistochemistry, and evaluated its association with t(11;14) and overexpression of cyclin D1. Nuclear staining of sox11 was observed in 54 of 57 (95%) mantle cell lymphomas, including 52 of 53 (98%) classical and 2 of 4 variant types. Two of the three mantle cell lymphomas negative for nuclear sox11 staining were analyzed and were positive for t(11;14). All other B-cell lymphomas (114 cases) showed variable positive staining in the cytoplasm, but no nuclear positivity. Sox11 was then examined in plasma cell myeloma and hairy cell leukemia as a subset of plasma cell myeloma carry t(11;14) and overexpress cyclin D1, and cyclin D1 is overexpressed in a subset of hairy cell leukemia independent of t(11;14). We found no nuclear staining of sox11 in 30 plasma cell myelomas examined, including 12 cases with t(11;14)(q13;q32). It is interesting that intense nuclear staining of sox11 was present in a subset of hairy cell leukemias (5 of 10), and was associated with the overexpression of cyclin D1. Our results indicate that the nuclear expression of sox11 is highly associated with mantle cell lymphoma, but is independent of t(11;14)(q13;q32) in non-mantle cell B-cell neoplasms. Its association with the overexpression of cyclin D1 in hairy cell leukemia suggests that sox11 may be involved in the upregulation of cyclin D1 in this leukemia.