BACKGROUND & OBJECTIVE: Even with improvements of colorectal cancer (CRC) treatment strategies, this cancer still has an unfavorable outcome. The primary cause of CRC development and recurrence is chemoresistance. CD10 and Notch1 are among cancer stem cell regulators, and they have roles in cancer progression and chemoresistance. This research aims to evaluate the expression of Notch1 and CD10 in CRC and their relationship with different clinicopathological parameters using immunohistochemistry. METHODS: This retrospective study included 100 cases of colorectal carcinoma that were immunohistochemically stained using Notch1 and CD10 antibodies. Expression of Notch1 and CD10 was evaluated and compared with different clinicopathological parameters. RESULTS: Notch1 expression was detected in the tumor and stromal cells in 92% of the cases, while CD10 expression was seen in 31% of tumor cells 79% of stromal cells of the included cases. Their expressions in tumor cells were significantly associated with higher grade ( CONCLUSION: CD10 and Notch1 may have roles in colorectal carcinoma progression via induction of tumor invasion, metastasis and impairment of tumor response to therapy. CD10 and Notch1 could be used as biomarkers for aggressive CRC and may be considered for future target therapy.