Canine osteosarcoma (OSA) is the most common bone tumour in dogs and is characterized by massive genomic instability throughout the cancer genome. Using matched primary tumour and metastasis samples from 8 OSA cases, we identified 2 focally deleted (<0.2 Mb) novel candidate genes, cyclin-dependent kinase inhibitor 2B (CDKN2B) and the membrane associated guanylate kinase, WW and PDZ domain containing 2 (MAGI2), which have not been previously identified in canine OSA and may have roles in driving OSA tumour progression. We also identified highly similar genomic profiles between matched samples, which yielded a small list of candidate regions that may harbour genes that drive metastasis formation. This study identified potential therapeutic targets, prognostic markers and early detectors of metastasis, in addition to providing insight into the OSA tumour progression.