In conclusion, although our study has not ultimately confirmed the association between MTHFR gene polymorphism and breast cancer risk, it clearly shows the crucial key-role of mutant allele presence of both polymorphisms in relation to the risk of developing more aggressive biophenotypes and, just in the case of A1298C, an increased risk to develop lymph node metastasis. Here, MTHFR is linked to metastatic malignant neoplasm in the lymph nodes.