Colon cancer, as the leading cause of cancer- related death is a significant public health concern due to its increasing rate in Iran [41–44]. Many specific immunohistochemical and PCR markers have been identified for detecting colon primary and metastatic tumors. CD133 is one of the immunohistochemical markers which was first observed in stem cells [45–48]. This marker has been suggested to be effective in cell proliferation and differentiation of various cancers including colon [49–51]. Therefore, in this study, we purposed to evaluate the expressions of C D133 using immunohistochemically staining, also its relationship to clinic pathological features as well as the prognostic indicator in colon cancer. Our study demonstrated that the CD133 expression was significantly correlated with CRC histopathology such as gender tumor, stage and lymphatic vascular invasion (P = 0.044, P = 0.011, P = 0.002, respectively). The higher CD133 expression was found at advance tumor stage (III). But it did not affect other factors such as age, five-year survival and tumor location in this study. In the line with our study, there was no significant difference between positive and negative CD133 and tumor location in several previous studies [16, 31, 34, 52–54]. In contrary, our study result was different from a study in which CD133 expression was higher in the rectum colon . Also, similar to our result, in a study done by Kojima on samples from 189 patients with different stages of CRC using IHC, they concluded that CD133 overexpression occurred mainly in well- to moderately-differentiated tumors and was not correlated with recurrence-free survival . However, there was conflicting results with our study regarding the expression of CD133 IHC staining in CRC and it relationship with the clinic pathological factors [68,55]. Many studies have demonstrated that CD133 expression is correlated with survival, recurrence, metastases and chemotherapy resistance, and most studies support the hypothesis that high D133 expression is a poor prognostic marker. [56–57]. In addition, in contrast to our results, Pitule et al. showed that patients with high CD133 expression had longer disease-free survival interval . While our study as well as some other studies reported that CD133 was not significantly correlated with the survival time (5 years) [58–60]. Another study performed by Park on CRC 303 patients using immunhistchemical staining, showed that CD133 expression in CRC was significantly associated with five-year survival and tumor stage, but no with other clinical factors such as gender which was significantly related in our study. Moreover, they suggested Cd133 expression may consider as a more potential biomarker for prognosis or a high-risk feature in the stage II CRC patients . This result was not consistent with our results. Contrary to our results, the results of a meta-analysis of 37 studies done by Huang in 2018 demonstrated that higher CD133 expression was positively correlated with shorter overall survival, lymphatic vascular invasion, distant metastasis and poorer prognosis in CRC patients. They also assumed that this low 5-year survival rate that might play an important role in the progression of colorectal cancer in CRC patients, was due to sex hormone, genetic and epigenetic factors that is affected by the environment and lifestyle and a variety of therapies . In Rey study on 118 patients in 2020, CD133 expression was significantly associated with the tumor location (p = 0.002), but not with other clinic pathological factors such as gender, age, body mass. Also, the tumor location had impact on the survival of CRC patients. This was in line with two previous studies [45, 49, 51] but no with our study. In immunohistochemistry study of Kazama on 200 endoscopically resected colorectal polyps and 20 normal mucosae, they demonstrated that CD133 expression was associated with only the degree of tumor differentiation and tumor size but not with gender, age, tumor location. Apart from two factors including age and tumor location, the statistical result of the gender parameter was consistent with our results. So, CD133 might play an important role in tumor development. Finally, the difference of our results with other researches may be due to different geographical area or race.