Canine osteosarcoma is 20 times more frequent than pediatric osteosarcoma while also sharing many similar biologic features, including primary tumor location, microscopic metastatic disease at diagnosis, altered expression of key proteins such as ezrin, and genetic aberrations of p53, phosphatase and tensin homolog (PTEN), retinoblastoma 1 (RB1), hepatocyte growth factor receptor (MET) and v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2) [18,41]. Here, RB1 is linked to metastatic neoplasm.