Cold agglutinin disease (CAD) is a well-recognized complication of lymphoproliferative disorders. It has been previously recognized that cases of primary CAD frequently exhibit underlying malignant lymphoma in the bone marrow. Lymphoplasmacytic lymphoma is the most common subtype of malignant lymphoma; however, diffuse large B-cell lymphoma (DLBCL) has also been documented, albeit extremely rare. The current report presents a case of primary bone marrow DLBCL accompanying CAD. A 76-year-old male presented with fever and fatigue. Laboratory tests revealed anemia and elevated bilirubin and cold agglutinins with a titer of 8,192 at 4°C. Bone marrow biopsy demonstrated DLBCL and systemic surveillance failed to detect tumorous lesions or lymphadenopathy. Following R-THP-COP therapy, cold agglutinins titer was markedly decreased (by <4); however, malignant lymphoma relapsed and cold agglutinin levels increased again (4,096). This is the second documented case of primary bone marrow DLBCL accompanying CAD. Previously, malignant lymphoma exclusively involving the bone marrow, namely primary bone marrow lymphoma (PBML), has been recognized as a rare and aggressive subtype. The analyses of the present study revealed that the incidence of hemolytic anemia in primary bone marrow DLBCL may be high compared with conventional DLBCL. Therefore, additional analyses are required to clarify the clinicopathological features of PBML.