Context: Vitamin B6, which is known as pyridoxine, is used as a nutritional supplement for many therapeutic purposes in medical centers. Women's health is important because they are assumed as the guarantors of health in societies. Breast pain is a common complaint in women of reproductive age and one of the most common reasons for women’s referral to health centers. The present study reviewed the impact of vitamin B6 on breast pain. Evidence Acquisition: In order to gather relevant articles, the databases of IRCT, Iran Doc, SID, MagIran, Medline, Cochrane, Embase, PubMed, Scopus, Science Direct, and Web of Knowledge were searched from 1980 up to July 2019. Keywords were extracted from MeSH, which included "Pyridoxol", "Rodex”, "PLP", "Pyridoxal-5-Phosphate", "Pyridoxine Hydrochloride", "Pyridoxine", "Vitamin B6", "Mastodynia", "Mammalgia", "Breast Pain", (Pain AND Breast), "Mastalgia", "Cycle Mastalgia", and "Non-Cycle Mastalgia". The same keywords were also searched in Persian databases. All selected studies had control and intervention groups and compared the pain-relieving effects of vitamin B6 with that of other therapies or placebo. Results: Among 338 examined articles, seven fulfilled our inclusion criteria and were included in the review. The results showed that vitamin B6 was more effective than placebo in improving breast pain even at low doses. Conclusions: Vitamin B6 is effective in relieving breast pain. However, there are also other supplements and medications to treat breast pain, so some factors like cost-effectiveness, availability, and side effects should be considered to choose a suitable agent.