BackgroundOsteosarcoma is a malignant bone neoplasia that has high welfare consequences for affected dogs. Awareness of breed and canine conformational risk factors for osteosarcoma can assist with earlier diagnosis and improved clinical management. Study of osteosarcoma in dogs also offers translational value for humans. Anonymised clinical data within VetCompass on dogs under primary veterinary care in the UK were searched for osteosarcoma cases. Descriptive statistics reported overall and breed-specific prevalence. Risk factor analysis used multivariable logistic regression modelling.ResultsFrom 905,552 study dogs, 331 osteosarcoma cases were confirmed yielding a one-year period prevalence of 0.037% (95% CI: 0.033–0.041). Breeds with the highest annual prevalence were the Scottish Deerhound (3.28%, 95% CI 0.90–8.18), Leonberger (1.48%, 95% CI 0.41- 3.75), Great Dane (0.87%, 95% CI 0.43- 1.55) and Rottweiler (0.84%, 95% CI 0.64–1.07). The median age at diagnosis was 9.64 years (IQR: 7.97–11.41).Following multivariable modelling, 11 breeds showed increased odds of osteosarcoma compared with crossbred dogs. Breeds with the highest odds included Scottish Deerhound (OR 118.40, 95% CI 41.12–340.95), Leonberger (OR 55.79, 95% CI 19.68–158.15), Great Dane (OR 34.24, 95% CI 17.81–65.83) and Rottweiler (OR 26.67, 95% CI 18.57–38.29). Compared with breeds with mesocephalic skull conformation, breeds with dolichocephalic skull conformation (OR 2.72, 95% CI 2.06–3.58) had increased odds while breeds with brachycephalic skull conformation showed reduced odds (OR 0.50, 95% CI 0.32–0.80). Chondrodystrophic breeds had 0.10 times the odds (95% CI 0.06–0.15) compared with non-chondrodystrophic breeds. Increasing adult bodyweight was associated with increasing odds of osteosarcoma.ConclusionsThe current study cements the concept that breed, bodyweight and longer leg or longer skull length are all strong risk factors for osteosarcoma in dogs. With this awareness, veterinarians can update their clinical suspicion and judgement, breeders can select towards lower-risk animals, and researchers can robustly define more useful study populations for fundamental and translational bioscience.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40575-023-00131-2.