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Objective-To determine factors predicting survival in dogs with high-grade multicentric lymphoma. Design-Retrospective cohort study. Animals-i 27 dogs with high-grade multicentric lymphoma evaluated at 4 veterinary hospitals from 2000 to 2009. Procedures-Records were reviewed to identify dogs with completely staged high-grade multicentric lymphoma treated with chemotherapy. Data collected included signalment, history, hematologic findings, tumor characteristics, treatment, and outcome. Long-term survival was defined as surviving > 2 years after diagnosis. Variables were analyzed for associations with dogs living > 2 years. Results-Among the 127 enrolled dogs, 13 (10%) survived >2 years with a median survival time of 914 days (range, 740 to 2,058 days). Survival rates at 3, 4, and 5 years were 4%, 3%, and 1%, respectively. At diagnosis, 11 of the 13 long-term survivors had a body weight 10 kg, PCV 35%, absence of ionized hypercalcemia, centroblastic lymphoma, immunophenotype B, absence of bone marrow involvement, and lymphoma stages I through IV and were not previously treated with corticosteroids.The same combination of factors was present in 26 of 114 (23%) dogs surviving ⩽ 2 years, yielding a negative predictive value of 978% for long-term survivors. Four of the 6 long-term survivors that died during the study died of another cancer; 3 of them had osteosarcoma. Conclusions and Clinical Relevance-Absence of the aforementioned combination of variables at diagnosis may help identify dogs with lymphoma that will not survive > 2 years. Other types of neoplasia, in particular osteosarcoma, may develop in long-term-surviving dogs. [ABSTRACT FROM AUTHOR]