Lymphoma is a severe condition characterized by the proliferation of neoplastic lymphoid cells. A 4-year-old female mongrel dog presented with solitary lymph node enlargement. Significant right prescapular lymphadenopathy and abdominal enlargement were observed during physical examination. A complete blood count revealed lymphocytosis, and a peripheral blood smear revealed lymphoblastosis and Mott cells. Fine needle aspiration cytology (FNAC) of the right prescapular lymph node revealed a predominant population of lymphoblasts and Mott cells. Based on the FNAC and blood smear results, the patient was diagnosed with leukemic state multicentric B-cell lymphoma with Mott cell differentiation. Subsequent PCR for antigen receptor rearrangement and flow cytometry revealed that the patient exhibited cross-lineage rearrangement (CLRA) and lineage infidelity (LI), respectively. CHOP-based chemotherapy was initiated, however, the patient’s disease was progressive. The patient died three months after the initial presentation. Mott cell differentiation in canine B-cell lymphoma (MCL) has rarely been reported in the veterinary literature and seems to show an unusual clinical course. To the best of our knowledge, no reports of MCL with CLRA and LI exist. We report the clinical features, diagnosis, and treatment of MCL with CLRA and LI.