Introduction: Breast carcinoma (BC) is one of the most common cancer-related mortality among women worldwide. S100A9 and S100A8 are calcium-binding proteins involved in BC metastasis. Toll-like receptors (TLRs) are membrane-bound proteins that play a vital role in immune systems and carcinogenesis through inflammatory cytokines. Objectives: We aimed to evaluate of S100A8, S100A9 and TLR5 in breast carcinoma by IHC, their gene expression by PCR and investigate their correlation with clinicopathological characters and hormone status. Materials and methods: This study was done in Biochemistry & Molecular Biology and Pathology Departments, Zagazig University, Egypt. Biopsy was taken from 72 patients with invasive breast carcinoma cases admitted to Surgery Department, Zagazig University, between January 2018 and January 2021. 72 breast biopsies were obtained from adjacent normal breast (as a control). IHC, gene expression by q real-time PCR using S100A8, S100A9 and TRL5. Results: Positive S100A8, S100A9, TLR5 were 81.9%, 76.4%, 86.1% respectively with statistically significant association between advanced stage, presence of lymph node metastasis, ER.PR status and HER2 negative expression. Conclusiones: Based on our findings, we postulated that S100A8, S100A9, TLR5 play an important role in progression of BC and can be used as novel molecular targets for earlier BC detection and prediction for future therapies in breast carcinoma. (c) 2021 SESPM. Published by Elsevier Espana, S.L.U. All rights reserved.