Osteosarcoma is a malignant cancer that carries a very poor prognosis in most large breeds of dogs. The standard of care treatment for osteosarcoma is surgery followed by chemotherapy. Unfortunately, a large number of these osteosarcomas undergo early metastasis (spread) even with early surgical intervention and chemotherapy. Infections of the surgery site, especially when limb-sparing surgery is used, have been known to stimulate the immune system post-operatively in dogs, resulting in improved survival. Since overall survival is bleak in patients with osteosarcoma, developing an osteosarcoma cancer vaccine holds promise as an adjunct treatment to surgery and chemotherapy. In a previous study of 400 dogs with melanoma we showed that a vaccine containing the ganglioside (GD3) causes a measurable immune response in normal dogs and dogs with melanoma, and prolonged survival. In this study, 40 dogs with osteosarcoma presenting to the University of Florida Small Animal Hospital will be randomly assigned to two treatment groups. Twenty dogs will be vaccinated using a ganglioside-based cancer vaccine following standard of care treatment. The outcome of the dogs receiving the vaccine plus standard of care will be compared to 20 dogs who receive standard of care without vaccination. Vaccines will be administered monthly for 4 treatments and the dogs monitored every 3-6 months for life or until lost to follow-up. The outcome of this study will help us understand the immune process associated with cancer vaccines for osteosarcoma and with an ultimate goal to improve survival for dogs with this aggressive form of cancer.