Background: Breast cancer (BC) is the most frequently diagnosed life-threatening cancer in women and the second leading cause of cancer death among women worldwide. The present conventional clinicopathological factors remain insufficient to evaluate the substantial prognosis of this disease. Midkine is a heparin-binding growth factor. It is upregulated in many types of cancer. Aim of the work: The aim of this study was to through light on the role of serum midkine level in breast cancer patients and its relation to the conventional tumor marker CA 15-3. Subject and method: This study was conducted on 40 newly diagnosed breast cancer patients (Group I) and 20 apparently healthy control subjects (Group II). Complete history, clinical examination, mammography and histopathological examination of breast cancer with immunohistochemical study were performed. Serum midkine level was assessed by double antibody sandwich assay technique(ELISA) by using human midkine ELISA kit also CA 15-3 level was assessed by using an automatic immune assay analyzer (TOSOH AIA system). Results: The present study revealed a statistically significant difference between breast cancer patients (Group I) and healthy control (Group II) regarding serum midkine level. Serum midkine level showed a statistically significant difference with stage of breast cancer, menopausal status and CA 15-3 serum level. There was no statistically significant difference regarding age, family history of breast cancer, parity, breastfeeding and history of oral contraceptive pills (OCPs) intake. Conclusions: This study showed that midkine might be a diagnostic and prognostic biomarker for breast cancer.