INTRODUCTION: Osteoprotegerin (OPG), encoded by the METHODS: A comprehensive literature search was conducted using PubMed Medline, Google Scholar, and ScienceDirect. Only full-text English publications from inception to September 2024 were included. RESULTS: Studies have demonstrated that certain SNPs in the OPG gene, specifically CONCLUSIONS: In this review, the role of OPG in breast cancer is examined. OPG has a multifaceted role in breast cancer tumorigenesis and exerts its effects through genetic variations (SNPs), interactions with TNF-related apoptosis-inducing ligand (TRAIL), and the modulation of the pro-tumorigenic microenvironment effects of angiogenesis, cell survival, and metastasis. Additionally, OPG's dual role as a tumor suppressor and promoter serves as a possible therapeutic target to enhance apoptosis, limit bone metastasis, and modulate the tumor microenvironment. Whilst much is now known, further studies are necessary to fully delineate the role of OPG.