Background: Recently, the predictive usefulness of variations in cancer antigen CA15-3 for breast cancer (BC) has received much attention. Objective: This study aimed to assess the relationship between the kinetics of the serum level of CA15-3 and the outcome of patients with non-metastatic BC. Patients and methods: This prospective single center trial was carried out in Medical Oncology Department, South Egypt Cancer Institute (SECI), Assiut University, on 75 female patients with non-metastatic BC patients. The serum level of CA15-3 was evaluated via Roche Elecsys at three time points (pre-operative, post-operative, and after one year of follow up). Results: Serum CA15-3 concentration showed a significant reduction from pre- to post-operative time, from pre- to after one year of follow up and from post-operative time to after one year of follow up (P< 0.001). No Significant relation was observed between CA15-3 and the clinic-pathological data of the studied non-metastatic BC patients. Also, CA15-3 level had no role in the survival outcome of the studied cases. Conclusion: The finding of the current study indicated that it is not necessary to mutually examine the pre- and post-operative serum level CA15-3 to evaluate its role as this will not add much more clinical benefit, and that we culd examine the pre-operative serum CA15-3 concentration to avoid wasting time, effort and money.