Neoplasms of the urinary bladder account for 1-2% of malignancies in dogs, and transitional cell carcinomas (TCC) represent 73% of primary bladder tumors. The incidence of TCC in dogs is increased with geriatric age, female sex, and exposure to carcinogens (exacerbated by obesity). The Scottish Terrier and the Shetland Sheepdog are over-represented in the population of animals that develop TCC (18:1 and 4.5:1 ratios respectively). TCC in the dog is a highly metastatic tumor that has historically responded poorly to surgical and medical therapy. Presented is the case of a 9-year-old, male castrated Shetland Sheepdog that was diagnosed with TCC of the urinary bladder. A subtotal resection of the tumor was performed and the patient was treated with piroxicam and mitoxantrone. Three and a half months following surgical debulking there was no evidence of local recurrence, lymph node involvement, or distant metastasis. Piroxicam has been used alone and in combination with traditional chemotherapeutic agents for the treatment of TCC in dogs. Though remissions occur with Piroxicam as a single agent, responses have been more favorable when combined with mitoxantrone. Piroxicam does not kill in vitro cultures of tumor cells at physiologically achievable levels, and it is presumed that its anti-tumor action is depencent on its activity as an inhibitor of cyclooxygenase. It is likely that piroxicam influneces tumor survival by interrupting prostaglandin-mediated modulation of apoptosis, neo-angiogenesis, and proliferation.