Canine mammary tumors (CMTs) represent a serious issue in worldwide veterinary practice and several risk factors are variably implicated in the biology of CMTs. The present study examines the relationship between risk factors and histological diagnosis of a large CMT dataset from three academic institutions by classical statistical analysis and supervised machine learning methods. Epidemiological, clinical, and histopathological data of 1866 CMTs were included. Dogs with malignant tumors were significantly older than dogs with benign tumors (9.6 versus 8.7 years, p < 0.001). Malignant tumors were significantly larger than benign counterparts (2.69 versus 1.7 cm, p < 0.001). Interestingly, 18% of malignant tumors were smaller than 1 cm in diameter, providing compelling evidence that the size of the tumor should be reconsidered during the assessment of the TNM-WHO clinical staging. The application of the logistic regression and the machine learning model identified the age and the tumor’s size as the best predictors with an overall diagnostic accuracy of 0.63, suggesting that these risk factors are sufficient but not exhaustive indicators of the malignancy of CMTs. This multicenter study increases the general knowledge of the main epidemiologica-clinical risk factors involved in the onset of CMTs and paves the way for further investigations of these factors in association with CMTs and in the application of machine learning technology.

Advances in tumour research are crucial, and comparative oncology can improve the knowledge in several ways. Dogs are not only models of specific naturally occurring tumours but can also be sentinels of environmental exposures to carcinogens, as they share the same environment with their owners. The purpose of this work was to describe the data collected by The Italian Network of Laboratories for Veterinary Oncology in the first 9 years of activity (2013–2021) and to evaluate their potential epidemiological significance. Frequencies of tumour topographies and main morphologies in dogs were described, analysed and compared, calculating age-adjusted proportional morbidity ratios and considering several risk factors (breed, sex, period and region of residence). These observations allowed us to highlight differences not only in morphology and topography of some tumours but also to formulate hypotheses on the potential role of some risk factors, e.g., neutering/spaying or geographical location. In our opinion, the results of this case series confirm the importance of initiating and consolidating animal cancer registration initiatives that would facilitate the possibility of conducting multicentric collaborative studies to deepen the knowledge of the epidemiology of tumours in dogs from a comparative perspective.