Aim: This study aimed to demonstrate misregulation of KMT2B gene expression in breast cancer tissue. Materials & methods: Cancerous and marginal tissue samples were collected from 43 female patients. After RNA extraction and cDNA synthesis, quantitative-PCR was used to evaluate the expression level of the KMT2B gene. REST, Sigma plot and SPSS software were used to analyze data. Results: KMT2B gene expression was significantly decreased in tumor tissue compared with marginal tissue (p = 0.02). No significant correlation was found between expression levels of KMT2B and clinical parameters of patients (p > 0.05) Conclusion: Our study demonstrated that downregulation of KMT2B is associated with breast cancer and its misregulation may play an important role in tumorigenesis.