Objective <p>Chemotherapeutic agents can induce morphologic changes in erythrocytes, leukocytes, and platelets in peripheral circulation. However, the cytomorphologic alterations associated with chemotherapy administration in circulating hemic cells are minimally characterized in dogs. Study objectives were to (1) assess differences in erythrocyte, leukocyte, and platelet morphologies and CBC metrics between healthy matched control dogs and dogs with multicentric lymphoma and (2) evaluate alterations in hemic cell morphology and CBC metrics in dogs with multicentric lymphoma being treated with multiagent CHOP chemotherapy regimen.</p> Results <p>Dogs with multicentric lymphoma (<i>n</i> = 20) had no differences in frequency and magnitude of hemic cell cytomorphology compared to control dogs (<i>n</i> = 20). However, lymphoma dogs had higher leukocyte, neutrophil, and monocyte counts. As dogs with lymphoma progressed through CHOP therapy, no differences in leukocyte or platelet cytomorphology were observed. The frequency and magnitude of erythrocyte polychromasia and were different between multiple chemotherapy timepoints. No morphologies consistent with dysplastic change were observed for any lineages. Differences in several erythrocyte, leukocyte, and platelet CBC indices were also observed. Atypical cytomorphologic abnormalities in circulating erythrocytes, leukocytes, and platelets, with the exception of leukemic cells, may be infrequent findings in dogs with multicentric lymphoma being treated with CHOP chemotherapy.</p>