CD133 is a transmembrane glycoprotein and is considered the most common cell surface marker to identify cancer stem cells in hematological and solid tumors, including breast cancer. To evaluate the impact of immunohistochemical expression of CD133 on response rate and survival in metastatic breast cancer, as well as to correlate it with various demographics and clinicopathological characteristics. One-hundred metastatic breast cancer patients were prospectively recruited at the Medical Oncology Department at South Egypt Cancer Institute during the period from January 2018 to January 2020. There was a statistically significant correlation between CD133 positive patients with various adverse clinicopathological parameters such as high grade (p= 0.013), higher tumor (p= 0.001), and nodal staging (p= 0.024) during a median follow-up time of 17 months. In addition, Cases with CD133 positive expression had a significantly lower survival time than those with negative expression (3-years OS 37.4% versus 85.5%, p= 0.024). Regarding the response rate, CD133 positive patients had a lower response rate than negative patients (50% versus 54%, p= 0.012). Positive CD133 is correlated with poor prognosis in metastatic breast cancer patients.