Abdominal lymph node enlargement is frequently noted sonographically. Certain sonographic features can be used to suggest whether lymphadenopathy is more likely benign or malignant. Specific changes in size, shape, echogenicity, and Doppler flow patterns have an association with malignancy. In this retrospective case–control study, the association between abdominal lymph node heterogeneity and malignancy was evaluated. Twenty-three canine and 18 feline patients with ultrasonographically heterogeneous abdominal nodes were evaluated for presence of benign or malignant lymphadenopathy. Controls were animals with lymph node enlargement of uniform echogeneity. Twenty-one (91%) of heterogeneous canine lymph nodes were malignant, and there was a significant association between heterogeneity and malignancy in canine abdominal lymph nodes (P=0.024). Seven (63%) heterogeneous feline lymph nodes were malignant, with no significant association between heterogeneity and malignancy (P=0.537).