ABSTRACT Background: Colorectal cancer (CRC) is the 3rd most prevalent diagnosed cancer and the 4th leading cause of cancer-related deaths globally. Nodal staging is significantly more essential in rectal cancer that detects most the therapy options. Objectives: This study aimed to evaluate CD133 expression in the colorectal carcinoma stage III using immunohistochemistry as well as its relationship to clinicopathological characteristics and patient outcomes. Patients and Methods: The study includes 60 cases with stage III CRC five years after surgical removal of the tumor and regular follow-up with the Departments of Medical and Clinical Oncology where clinicopathological and prognostic data are collected from the archives. The patients were classified into two groups, GI includes 22 CRC patients with relapse, and GII includes 38 CRC patients without relapse. Sixty archive paraffin blocks of primary resection and metastatic lymph nodes were extracted from the archives of the Pathology Department processed for CD133 immunohistochemistry. CD133 expression levels were assessed, analyzed, and correlated with clinicopathological and prognostic criteria. Results: Positive CD133 expression was significantly linked with old age ( P=0.034 ), large tumor size ( p < 0.001), perineural invasion (p = 0.0017), lympho-vascular invasion ( P < 0.001 ), high-grade ( p < 0.001 ), resistance to chemotherapy (p = 0.011), lymph nodes metastasis and relapse (p = 0.005*) and DFS (p = 0.005) Conclusion: CD133 expression in colorectal carcinoma is related to tumour progression and is considered a marker of poor prognosis and a strong indicator of relapse and poor survival. Moreover, CD133 stem cell marker may act as a targeted therapy in chemotherapeutic resistance patients with colorectal carcinoma.