The need for more appropriate animal models in cancer research has led, over the past 20 years, to consider pets with spontaneously occurring neoplasms as a valuable and still under used resource. The role of companion animals in the struggle to eradicate cancer can be multiple: they may act as environmental sentinels, help in gaining insights on tumor biology and finally may be enrolled in therapeutic trials which might act as a bridge to the clinic applications. This paper will focus on the most valuable spontaneous neoplasms in companion animals and will analyze the potentials of each histotype as a model for basic research and for new therapeutic strategies. It is conceivable that in the next years comparative oncology will play a paramount role in translational medicine allowing a rapid flow of data from laboratories to clinical application in humans.