Objective: Breast cancer is the leading cause of death among women in many countries. Numerous factors serve as oncogenes or tumor suppressors in breast cancer. The large family of Tripartite-motif (TRIM) proteins with ~ 80 members has drawn attention for their role in cancer.TRIM3andTRIM16have shown suppressive activity in different cancers. This study aimed to evaluate the expression ofTRIM3andTRIM16in cancerous and normal breast samples and to investigate their association with different clinical and pathological parameters.Results: qRT-PCR was utilized to determine the gene expression ofTRIM3andTRIM16. The expression ofTRIM3andTRIM16genes in tumor samples were significantly reduced to 0.45 and 0.29 fold, respectively.TRIM3andTRIM16genes expression were both positively correlated with the invasion of breast cancer.TRIM3gene expression was associated with tumors’ histological grade. However, no significant association was found between the expression of the genes and tumor size, stage and necrosis. The expression ofTRIM3andTRIM16are significantly reduced in breast cancer tissues. Besides, the expression of bothTRIM3andTRIM16genes significantly plummet in lymphatic/vascular and perineural invasive samples. Hence, we suggest a potential tumor suppressor role forTRIM3andTRIM16in breast cancer.