A 10-year old female spayed Springer Spaniel being treated for chronic myeloid leukemia (CML) previously diagnosed in 2015, was presented to Cornell’s Oncology Service 5/30/2017 for evaluation of lethargy and newly-developed peripheral lymphadenopathy. On 2/2/15, the patient was first presented to Cornell’s Oncology Service for progressive lethargy, inappetence, and weight loss with a persistent leukocytosis. Diagnostic work-up revealed a leukocytosis characterized by a mature neutrophilia with a left shift to myelocytes, myeloid and megakaryocytic hyperplasia with mild dysplastic changes in myeloid cells and megakaryocytes, and 3% myeloblasts on a bone marrow aspirate, myeloid hyperplasia with pockets of precursors on splenic histopathologic sections, and no evidence of underlying inflammation, infection, or other neoplasia; a diagnosis of CML was made. On 5/11/15, the patient was started on hydroxyurea for treatment of CML. Lethargy, weight loss, and leukocytosis resolved with treatment. The patient remained in remission on hydroxyurea chemotherapy until representation on 5/30/17 for lethargy and peripheral lymphadenopathy. Diffuse peripheral and internal lymphadenopathy was found on physical examination, thoracic radiographs, and abdominal ultrasound. Cytologic results of a lymph node aspirate were indicative of hematopoietic neoplasia and immunophenotyping of the aspirate with flow cytometry confirmed B-cell lymphoma. A bone marrow aspirate showed persistent myeloid hyperplasia compatible with the previous diagnosis of CML and no evidence of lymphoma infiltration or a myeloid blast crisis. Stage IIIa B-cell lymphoma was diagnosed. The patient was started on L-CHOP chemotherapy (L-asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisone) for B-cell lymphoma on 6/5/17. The patient initially responded to chemotherapy, but the disease progressed on 8/21/17. Rescue chemotherapy with MOPP (mustargen, vincristine, procarbazine, prednisone) was started on 8/29/17. After 2 weeks of stable disease, the lymphoma progressed again and changes on a blood smear were consistent with progression of CML. The patient was given Tanovea (rabacfosadine) on 9/12/17. Two weeks later on 10/2/17, the lymphoma had progressed again. Cytarabine and L-asparaginase were administered, but no response was seen. Due to progression of disease in the face of chemotherapy and concerns regarding quality of life, the patient was euthanized on 10/15/17, 5 months after diagnosis of B-cell lymphoma and 2.5 years after diagnosis of CML. This case is an interesting example of canine lymphoma diagnosis and treatment, complicated by historical and persistent CML. Discussion will focus on the diagnosis and treatment of hematopoietic neoplasms in dogs and comparative oncology.