B-cell lymphoma is one of the most common cancers in dogs. Although current tests can diagnose lymphoma, they do not fully explain why tumors behave or respond differently to treatment. Genetic testing may help divide these cancers into more meaningful groups, but mutations must first be confirmed in an independent population. In an earlier study of five dogs, we used whole-genome sequencing to identify genetic changes found in both lymphoma cells and plasma (a component of blood). Several known lymphoma-associated genes were detected, along with less-studied candidates. As that study included few dogs, some findings may represent rare changes or technical artifacts rather than truly recurrent alterations. This study will develop a focused, high-depth sequencing panel containing established lymphoma genes and promising new candidates. We will test it on archived lymph node tissues from up to 50 dogs with diffuse large B-cell lymphoma, together with normal lymph nodes and available fine-needle aspirate smears. Laboratory and computational controls will identify DNA damage caused by preservation, and selected findings will be checked using digital PCR. We will determine how often each candidate gene is altered and whether the same findings can be detected in minimally invasive cytology samples used in clinical practice. The final products will be a rigorously evaluated list of recurrent tumor-associated alterations and an assay suitable for preserved tissues. These results will support future studies of lymphoma classification, prognosis, treatment response, and less-invasive testing in dogs, while strengthening the dog as a comparative model for human lymphoma.