The authors provide a review of current knowledge of lymphocytosis in nonneoplastic conditions. They conclude that the list of major differentials for persistent nonneoplastic lymphocyte expansion in dogs and cats is short and that most of these conditions are relatively uncommon. Persistent lymphocytosis of small, mature, or reactive lymphocytes is most commonly the result of chronic lymphocytic leukemia or lymphoma. The first step in distinguishing nonneoplastic from neoplastic lymphocytosis is immunophenotyping by flow cytometry to determine the phenotypic diversity of the circulating cells. Clonality testing using the polymerase chain reaction for antigen receptor rearrangements assay is a useful second step in cases in which the phenotype data are equivocal. Once the diagnosis of malignancy has been established, the immunophenotype also provides prognostic information in dogs.