Abstract Background: The most frequent cause of cancer deaths throughout the world is breast cancer (BC). Therefore, preventing, diagnosing and treating BC has gained importance. Calcium-binding S100 group proteins are coded in the chromosome 1q21 and have many members. It is claimed that S100A12 and S100A9 play an important role in the development of cancer. S100A12 is normally expressed in neutrophil granulocytes, and from lymphocytes and monocytes in small amounts. S100A12 is closely related to inflammation and vascular invasion by tumor cells, and causes excessive inflammation and vascular invasion causes tumor recurrence and metastasis. S100A9 protein is found in human epithelial cells and cytosols in phagocytes and regulates the motility of phagocytes and activity of target proteins through interaction with danger signal molecules. Furthermore, it has also been stated that it is possible that it regulates the cellular growth through interaction with p53 like other S100 proteins and can modulate metastasis of malignant tumors. In this study, we aimed at diagnostic and clinic-pathological importance of serum levels of S100A9 and S100A12 with known cytokin-like pro-inflammatory effects in BC. Material: A total number of 45 patients with breast cancer were first admitted in the study. Sixteen age-matched healty women were enrolled in to this study. All the samples were analyzed with enzyme-linked immunosorbent assay for serum S100A9 and S100A12 levels before starting the systemic chemotherapy. The characteristics of the breast cancer patients with respect to age, weight, height, menopausal status, histopathological type, tumor size, tumor lymph node metastasis, tumor grade, and estrogen receptor (ER) and progesterone receptor (PR) and HER2, lymphovascular invasion (LVI), perineural invasion (PNI) status and stage were collected for data analyses. Clinicopathologic characteristics of BC and other blood parameters were compared in relation with serum S100A9 and S100A12 levels. Results: While the serum S100A9 levels were found significantly higher as compared to healthy individuals (190.85±32.29 and 92.72±54, respectively) (p=0.001), it was observed that there were no differences in S100A12 (120.50±15.78 and 112.21±10.46, respectively) (p=0.056) levels. As regards the subgroup analysis in BC patients, no statistically significant results were found in body mass index, smoking, menopause status, histopathologic type, grade, biological subtype of BC, tumor size, presence of lymph node metastases, LVI, PNI and stage. As regards the blood parameters and serum S100 A9, while only statistically significant results were found with anemia (209.05±33.12 and 181.75±28.21, respectively) (p=0.005), no statistically significant results were found with leukocytosis, thrombocytosis and tumor markers. Conclusion: In this study, while we found the level of S100A9, which has a potential cytokine-like function in inflammation, significantly higher, we could not find any increase in S100A12 level. Therefore, it is possible that S100A9 can play a key role in inflammation-related BC. We therefore suggest that serum S100A9 can be the target marker in breast cancer both as a diagnostic tool and to suppress inflammation in treatment. Citation Format: Gunaldi M, Okuturlar Y, Üstüngüler A, Akarsu C, Kural A. Clinical importance of S100A9 and S100A2 in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-23.