A 13-year-old female spayed Maltese Dog was referred to the Cornell University Hospital for Animals’ Oncology Service for evaluation of probable lymphoma. On presentation, the dog was bright and alert with normal vital parameters. On physical examination, she had generalized peripheral lymphadenomegaly. Two small masses were palpable in her abdomen, which were confirmed to be enlarged lymph nodes with abdominal ultrasound. The major problem addressed was the patient’s lymphadenomegaly of which differential diagnoses included lymphoma (with a typical progression or a more indolent form of the disease), infectious diseases, immune-mediated diseases, or other hematopoietic tumors. In this particular case, diagnostic tests that would typically lead to an easy diagnosis of lymphoma did not prove straightforward. The patient was ultimately diagnosed with a stage IIIa B-cell lymphoma using a combination of history, physical exam findings, and PCR for antigen receptor rearrangement (PARR). She is undergoing treatment with a CHOP based protocol.