Aim: Despite the improved diagnosis and treatment methods in recent years, the number of new breast cancer cases does not reduce and the mortality rates are still so high. There are several proteins that play significant roles in carcinogenesis process and hold a great potential to be used as a marker of cancer diagnosis. A-Kinase Anchoring Protein 12 (AKAP12) regulates gene expression in cell cycle and apoptosis while B- cell Lymphoma 2 (BCL2) family proteins and inhibitors of apoptosis proteins are the major regulators of the apoptotic process. High mobility group box 1 (HMGB1) has multiple pro-tumor roles in tumor development. In our study, we aimed to determine the usability and sensitivity of AKAP12, BCL2 and HMGB1 proteins as a marker of breast cancer diagnosis, and further investigate the relationship among these proteins. Material and Methods: Between 2014 and 2017, a total number of 82 participants, 60 of them were diagnosed with early stage breast cancer and 22 healthy age-matched people as control group, were included in the study. Serum samples obtained from the groups were investigated in terms of AKAP12, BCL2 and HMGB1 levels by using Enzyme Linked Immuno-Sorbent Assay (ELISA) method. Results: Comparing the patient group with control groups, AKAP12, BCL2 and HMGB1 levels were found to be significantly higher in the patient group (p ¼ 0.009), (p < 0.001) and (p < 0.001), respectively. Conclusion: The findings of our results indicate that these proteins levels may be used as markers in the diagnosis and follow-up of breast cancer.