This chapter will focus on invasive urothelial carcinoma (InvUC). This form of urinary bladder cancer is one with the greatest need for improved patient outcomes and is also one in which the naturally occurring canine model offers tremendous opportunities to drive advances in treating and managing the disease. Canine InvUC closely mimics InvUC in humans in cellular and molecular features, molecular subtypes, immune response patterns, biological behavior including sites and frequency of metastasis, and response to therapy. In addition, the high breed-associated risk for InvUC in dogs, including a 20-fold increased risk in Scottish Terriers compared to dogs in other breeds, offers an unparalleled opportunity to test new strategies in primary prevention and secondary prevention in the form of early detection and early intervention. The canine model can complement experimental models that can be applied in more tightly controlled experiments, especially those designed to study specific mechanisms. This chapter will provide an overview of human and canine InvUC, summarize the similarities and differences between the species, and provide examples of areas where canine studies could be most impactful in improving the outlook for humans, as well as dogs.