Background & Objective: The regulator of chromosome condensation ۲ (RCC۲) and RAS-related C۳ botulinum toxin substrate ۱ (Rac۱) have been implicated in the promotion of breast cancer cell proliferation and migration. The signaling pathway involving p۵۳/RCC۲/Rac۱ has been proposed to contribute to the regulation of colon cancer metastasis. However, until now, this pathway has not been thoroughly investigated in breast cancer. This study seeks to explore the influence of immunohistochemical expression and the correlation among RCC۲, Rac۱, and p۵۳ in breast infiltrating ductal carcinoma (IDC).Methods: Immunostaining was performed on ۱۲۰ breast IDC specimens using RCC۲, Rac۱, and p۵۳ antibodies. Statistical analyses were conducted to examine the correlations between these antibodies.Results: A Positive expression of RCC۲, Rac۱, and p۵۳ was observed in ۱۱۶ (۹۶.۷%), ۱۲۰ (۱۰۰%), and ۳۳ (۲۷.۵%) of the breast cancer cases, respectively. RCC۲, Rac۱, and p۵۳ demonstrated association with poor prognostic parameters such as frequent mitoses, high Ki-۶۷ status, positive lymphovascular invasion (LVI), and advanced tumor stage. A highly significant direct correlation was found between each immunohistochemical marker and the other two markers. Shorter overall survival was linked to multifocal tumors (P=۰.۰۱۷), advanced tumor stage (T۳) (P=۰.۰۱۰), Luminal B subtype (P=۰.۰۱۵), progressive disease (P=۰.۰۰۳), positive Her۲neu status (P=۰.۰۰۸), and metastasis to distant organs (P<۰.۰۰۱). However, RCC۲, Rac۱, and p۵۳ did not exhibit a significant association with overall survival.Conclusion: The high expression levels of RCC۲, Rac۱, and p۵۳ in breast IDC suggest their potential role in tumor behavior. The association of RCC۲ and Rac۱ with poor prognostic parameters may serve as predictive indicators for aggressive tumors, thus implying that targeted therapy could be beneficial in the treatment of breast cancer.