Pleomorphic B cell lymphoma was detected in a small number of lymph nodes in an 8-year-old Holstein cow with persistent lymphocytosis associated with bovine leukemia virus (BLV). Necropsy showed enlargement of the left superficial inguinal and right deep inguinal lymph nodes. Large numbers of BLV copies were detected by real-time polymerase chain reaction analysis in the enlarged nodes, whereas little BLV was found in normal-sized lymph nodes. Histologically, the enlarged lymph nodes were occupied by diffusely growing pleomorphic cells. In a few other lymph nodes, in contrast, extensive areas of neoplastic mantle cells showing a transition to more malignant pleomorphic cells were observed. These virological and histological findings indicate that large numbers of viral copies may be closely related to transformation from neoplastic mantle cells to pleomorphic lymphoma cells. The current study supports the view that nodal pleomorphic B cell lymphoma is of mantle cell origin.