Sterile biopsy or fine needle aspirate (FNA) samples were available from 28 dogs (four dogs from cohort-I and 24 dogs in cohort-II) with a diagnosis of B-cell lymphoma at participating veterinary hospitals with owner consent under protocols approved by the University of Minnesota Institutional Animal Care and Use Committee (IACUC) and the Colorado Multiple Institutional Review Board. The 28 dogs were from 14 breeds, including six Golden Retrievers, four Labrador Retrievers, two Pembroke Welsh Corgis, two Standard Poodles, and one each of 10 other breeds, as well as four mixed breed dogs. The gender distribution was 50:50, and the average age was 8.6 years (median = 9 years, range 3 - 14). Normal tissue controls were obtained at the time of euthanasia from six healthy, purpose-bred, one-year-old female Beagle dogs that were part of an unrelated project. Collection of normal tissues was done under a protocol approved by the University of Minnesota IACUC. Sample preparation for histopathology, cytology, and flow cytometry was performed as described.17 (link) The final histopathological classification was determined by one author (VEV) with a consensus of three additional authors (DI, TDO, JFM) upon review of the specimens. Tumors were classified according to the modified WHO classification.18 They included 13 diffuse large B-cell lymphomas, four Burkitt-like lymphomas, two marginal zone lymphomas, two low-grade B-cell lymphomas of intermediate centrocytic cells with cleaved nuclei, one follicular lymphoma, and one anaplastic large cell lymphoma. Sufficient sample material was not available for histopathological analysis of five cases. An uncommon phenotype of canine B-cell lymphomas that express CD34 was previously reported.19 (link) Because it is unclear if this represents a unique subtype with distinct biology, inclusion criteria for samples was set as <5% CD34+ cells in the tumor populations to limit the confounding effects of this variable. NOD/SCID/IL-2Rγ−/− (NSG) mice were purchased from Jackson Laboratories (Bar Harbor, ME) and maintained under specific pathogen-free conditions according to institutional guidelines. Lymph node collection from dogs and xenotransplantation of canine lymphoma cells into conditioned, immunocompromised (NSG) mice were conducted with approval of the University of Minnesota IACUC.