Breast cancer is the most frequent spontaneous malignancy diagnosed in women and is characterized by a broad histological diversity. Progression of the disease has a metastasizing trend and can be resistant to hormonal and chemotherapy. Animal models have provided some understanding of these features and have allowed new treatments to be proposed. However, these models need to be revised because they have some limitations in predicting the clinical efficacy of new therapies. In this review, we discuss the biological criteria to be taken into account for a realistic animal model of breast cancer graft (tumor implantation site, animal immune status, histological diversity, modern imaging). We emphasize the need for more stringent monitoring criteria, and suggest adopting the human RECIST (Response Evaluation Criteria in Solid Tumors) criteria to evaluate treatments in animal models.