Breast cancer (BC) is the most commonly diagnosed cancer in Azerbaijan with increasing incidence every year. There were 41.9%-54.3% patients diagnosed with stage (s) III and IV for the period 2012-2016. BC is highly heterogeneous in its pathological characteristics, some cases showing slow growth with excellent prognosis, while others being aggressive tumors with early metastasis and recurrence. Therefore, definition of different markers play a crucial role in prognosis and determination of therapy in those group of patients. Evaluation of combination of markers such as CA 15-3 and Vitamin D (VD) may be beneficial in disease prognosis. This study, to our knowledge, is the first research to test those markers in patients with BC (we did not find any study describing this investigation in PubMed or any other medical database for the period 1963-2019). Purpose: To study the predictive and prognostic role of combination of CA 15-3 and VD in patients with BC. Materials and Methods: The combination of CA 15-3 (0-35U/ml and >35 U/ml ) and VD (5 levels 0-10, 11-20, 21-30, 31-50, >50 ng/ml) were measured in 362 patients for the period 2014-2019 at National Center of Oncology. In 78 patients level of CA 15-3 >35 U/ml and VD 0-10 ng/ml was determined; in 284 patients CA 15-3 and VD records were divided into 9 groups. Table 1. ECL method was used. Results: VD and CA 15-3 parameters were divided in two groups according to the stage of BC. 1. Among 78 patients with VD 0-10 ng/ml and CA 15-3 >35 U/ml-78% patients were diagnosed with stage IV, 22% patients with stage III, 0% patients with stage 0, I and II. Among 284 patients in control group 10% were diagnosed with stage IV, 43% patients with stage III, 39% with stage II and 7% with stage I, 1% patients with stage 0 BC. Table1. 2. In group of patients with VD 0-10 ng/ml and CA 15-3 >35 U/ml records stage 0, I, II, III and IV were diagnosed in 0%, 0%, 0%, 12% and 69% respectively. In other 9 groups - 100%, 100%, 100%, 88% and 31% respectively. Table2. Patients with high level of VD had a better results of treatment. Conclusion: Level of VD 0-10 ng/ml and CA 15-3 >35U/ml in patients with BC should be considered as a poor prognostic indicator. For visualizing the spread of tumor and determine the stage of the disease should be used the different breast diagnostic approaches, including positron emission tomography (PET/KT). For the best treatment results after cytotoxic therapy level of VD has to be monitored.