BackgroundSeveral observational studies have explored the relationships between multiple sclerosis (MS) and breast cancer; however, whether an association exists remains unknown.MethodsWe conducted a meta-analysis of observational studies and Mendelian randomization (MR) based on genetic variants to identify the relationship between MS and breast cancer. The observational studies were searched from PubMed, Embase, Web of Science, and Scopus to assess the relationship between MS and breast cancer from inception to 07 Nov 2022. Moreover, we explored the association between genetically pre-disposed MS and breast cancer risk based on an MR study. The summary analysis for MS from two separate databases [International Multiple Sclerosis Genetics Consortium (IMSGC), FinnGen] and the summary analysis for breast cancer from Breast Cancer Association Consortium.ResultsFifteen cohort studies involving 173,565 female MS patients were included in this meta-analysis. The correlation between MS and breast cancer was not statistically significant [relative ratio (RR) = 1.08, 95% confidence interval (CI) = 0.99–1.17]. In the MR analysis, we did not observe causal associations of genetically determined MS with breast cancer and its subtypes from both the IMSGC and FinnGen datasets.ConclusionThe meta-analysis of observational and MR based on genetic variants does not support the correlation between MS and breast cancer.