A 2-year-old creole filly was referred to us for evaluation because of the clinical suspicion of infection by Streptococcus equi. It presented with progressive weight loss and increased volume of the submandibular, retropharyngeal, and precrural lymph nodes. General clinical examinations and laboratory tests revealed dehydration, anemia, leukopenia, hyperfibrinogenemia, and thrombocytopenia. The initial treatment for equine adenitis did not achieve significant results, and new hematological and biochemical tests and lymph node cytology by puncture were performed. Cytology revealed cells compatible with neoplastic lymphocytes, resulting in the suspicion of lymphoma. The animal died from general weakness and was sent for autopsy. Macroscopically, generalized lymphadenomegaly and splenomegaly were observed, with multiple nodules and tumor lesions in the splenic parenchyma. There was an irregular nodule in the medullary layer of the right kidney. The liver and lungs were slightly enlarged, with petechiae and multifocal suffusions. Histopathological evaluation of different organ specimens revealed intense proliferation of the neoplastic lymphoid cells, invading the adjacent tissues, with moderate cellular pleomorphism. Immunohistochemistry of the lymph node sections with neoplastic infiltration revealed multicentric T-cell lymphoma. In horses, cases of lymphomas are rare and should be differentiated from other causes that induce lymphadenomegaly in this species.