One hundred ninety six dogs with spontaneously occurring lymphoproliferative disorders were immunophenotyped. Dogs with lymphoma (175) were determined to be derived from B-cells in 134/175 (76%), T-cells in 38/175 (22%) and 3/175 (2%) were null cells (non-reactive with any canine-specific lymphocyte antibody). Dogs with T-cell lymphomas were at significantly higher risk of relapse and early death compared with B-cell lineage lymphoma following therapy (52 vs. 160 days; p < 0.001 and 153 vs. 330 days; p < 0.001, respectively). Hypercalcemia was associated only with CD4+ lymphomas. A nonimmunoglobulin B-cell marker (B5), expressed in 95% of nonneoplastic lymphocytes, was expressed at a reduced level in 63% (64/104) of dogs with B-cell lymphoma. Dogs with lymphoma in which the B5 antigen was expressed below normal levels experienced shorter progression free survival (125 vs. 202 days; p < 0.05) and overall survival times (203 vs. 385 days; p < 0.05) than dogs with B-cell lymphoma in which the B5 antigen was expressed normally. Chronic lymphocytic leukemia in dogs was primarily associated with a CD8+ phenotype (8/12) and acute lymphoblastic leukemia was determined to be of either null cell (4/9) or T-cell (3/9) phenotype. Although canine and human non-Hodgkin's lymphoma are phenotypically similar, canine leukemia is phenotypically distinct from human leukemia. The development of canine-specific probes has facilitated a priori assessment of treatment outcome in dogs with lymphoma and may in the future contribute to the comparative understanding of leukemo- and lymphoma-genesis in these species.