BACKGROUND AND AIM: DCIS is the most common type of non-invasive breast cancer, accounting for about 15 to 30%. Proteome profile is used to detect biomarkers in the tissues of breast cancer patients by mass spectrometry. This study aimed to obtain the expression profile of DCIS proteome, and the expression profile of invasive biomarkers, and finally to introduce a dedicated biomarker panel to facilitate the prognosis and early detection for in situ breast cancer patients. METHODS AND MATERIALS: In this study, 10 patients with breast cancer (DCIS) were studied. Benign (marginal) and cancerous tissue samples were obtained from patients for proteomics experiments. Initially, all tissue proteins were extracted using standard methods, and the proteins were separated using two-dimensional electrophoresis. Then, the expression amount of the extracted proteins was determined by ITRAQ. The data were analysed by R software, and gene ontology was utilised for describing the protein in detail. RESULTS: 30 spots on gel electrophoresis were found in the tumor tissue group (sample), and 15 spots in the margin group (control) with P < 0.05. Healthy and cancerous tissue gels showed that 5 spots had different expression. VWF, MMP9, ITGAM, MPO and PLG protein spots were identified using the site www.ebi.ac.uk/IPI. Finally, protein biomarkers for breast tumor tissue with margin were introduced with the names of P04406, P49915, P05323, P06733, and P02768. DISCUSSION: There are 5 critical proteins in inducing cancer pathways especially complement and coagulation cascades. The hall markers of a healthy cell to be cancerous are proliferation, invasion, angiogenesis, and changes in the immune system. Hence, regulation of protein plays a key role in developing recurrence to breast cancer in margins.