Breast cancer (BC) is the most frequently diagnosed malignancy in women worldwide. Despite the wide variety of therapeutic methods for BC, their results are not satisfying, especially in triple-negative breast cancer (TNBC) patients. One of the main challenges in efficient oncology is achieving optimal conditions to evaluate a molecular genotype and phenotype of a tumor. Therefore, new therapeutic strategies are urgently needed. Animal models are an important tool for the molecular and functional characterization of BC, and for the development of targeted BC therapies. Zebrafish, as a promising screening model organism, has been widely applied in the development of patient-derived xenografts (PDX) for the discovery of novel potential antineoplastic drugs. Moreover, the generation of BC xenografts in zebrafish embryos/larvae allows for a description of the tumor growth, cell invasion, and systemic interaction between tumor and host in vivo without immunogenic rejection of transplanted cancer cells. Interestingly, zebrafish can be genetically manipulated and their genome has been fully sequenced. Genetic studies in zebrafish have described new genes and molecular pathways involved in BC carcinogenesis. Thus, the zebrafish in vivo model is becoming an exquisite alternative for metastatic research and for discovering new active agents for BC therapy. Herein, we systematically reviewed the recent cutting-edge advances in zebrafish BC models for carcinogenesis, metastasis, and drug screening. This article aims to review the current status of the role of the zebrafish (Danio reiro) in preclinical and clinical models of biomarker identification and drug targeting, and developments in personalized medicine in BC.