B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) may involve the bone marrow in nodular, interstitial, diffuse, or mixed patterns. However, B-cell CLL/SLL associated with large reactive germinal centers (the so-called interfollicular pattern) involving the bone marrow is not reported. We describe 2 examples of B-cell CLL/SLL that subtotally replaced the bone marrow with an interfollicular pattern. In both cases, the neoplasms were composed of small round lymphoid cells; proliferation centers also were present. The neoplasms surrounded large reactive germinal centers that were devoid of peripheral mantle zones. The germinal centers were paratrabecular and nonparatrabecular in case 1 and nonparatrabecular in case 2. Flow cytometry immunophenotypic studies done on bone marrow aspiration samples of both cases showed a uniform population of neoplastic cells positive for pan-B-cell antigens and the CD5 and CD23 antigens. Immunohistochemical studies done on bone marrow biopsy sections supported the flow cytometry results and demonstrated that the germinal centers were negative for BCL-2. B-cell CLL/SLL may rarely involve the bone marrow with an interfollicular pattern. Knowledge of this pattern will prevent confusion with follicle center lymphoma and large cell transformation, both of which initially were considered in the differential diagnosis of these cases.