ABSTRACTDiffuse large B‐cell lymphoma (DLBCL) is one of the most prevalent haematological malignancies in both humans and dogs, characterised in both species by significant clinical heterogeneity and limited prognostic predictability. With the introduction of next‐generation sequencing (NGS) technologies in veterinary medicine over the past decade, researchers have begun to elucidate the molecular basis of canine DLBCL (cDLBCL); however, much of the clinical heterogeneity associated with this tumour remains unexplained. In this study, we performed whole genome sequencing on 10 cDLBCL cases, all treated with chemo‐immunotherapy, which exhibited similar clinico‐pathological features but markedly different outcomes. Cases were classified as “poor” or “good” responders based on whether their lymphoma‐specific survival fell below or above the cohort's median. Protein‐coding variants and copy number aberrations unique to poor or good responders revealed novel candidate genes not previously identified in cDLBCL studies, while splicing, untranslated regions, and intronic variants were detected in genes already known to be recurrently mutated. In conclusion, our investigation has broadened the spectrum of potentially pathogenic variants implicated in cDLBCL, though further studies with larger cohorts are necessary to validate these findings.