Invasive bladder cancer results in over 10,000 deaths yearly in the United States alone. More effective therapy for invasive bladder cancer is clearly needed. As new cellular and molecular targets for therapy are identified, relevant animal models are needed to test new therapeutic strategies aimed at these targets prior to human clinical trials. The purpose of this review is to characterize spontaneous invasive transitional cell carcinoma of the urinary bladder (TCC) in dogs, to summarize the similarities and differences between canine and human invasive TCC, and to describe how canine TCC could serve as a relevant model of human invasive bladder cancer. Information was summarized from 102 dogs with TCC evaluated and treated at the Purdue University Veterinary Teaching Hospital, from a review of the Veterinary Medical Data Base, and from reports in the literature. Canine TCC was found to be very similar to human invasive bladder cancer in histopathologic characteristics, molecular features, biological behavior including metastasis, response to medical therapy, and prognosis. Differences between canine and human TCC were few, but included gender predilection with a male:female ratio of 2.8:1 in humans versus a male:female ratio of 0.5:1 in dogs. The location of the TCC within the bladder also differed: Most canine TCC was trigonal in location, whereas more than 50% of human TCC was in the lateral and posterior walls of the bladder. Considering the great similarity between invasive bladder cancer in humans and dogs, spontaneous canine TCC can be considered a relevant animal model of human invasive bladder cancer.