AIM: To analyze the expression of 8 putative cancer stem cell (CSC) markers within colorectal cancer tumor buds and to determine their prognostic impact in patients with this disease.METHODS: Immunohistochemistry was performed on 101 colorectal cancer resections for CK22 (to identify tumor buds) as well as CD133, CD166, CD24, CD44s, CD90, EpCAM, ALDH1, and ABCG5, and their expression within tumor buds was evaluated.RESULTS: CD90, CD44s, and CD133 expression in tumor buds was found in less than 5% of all cases.ALDH1, CD24, CD166 were expressed in 16.5%, 16.2%, and 34% cases, respectively, while ABCG5 and EpCAM expression was more frequent and found in 35% and 69% of cases, respectively.Of the 8 markers studied, EpCAM and ABCG5 positivity in tumor buds were significantly associated with poor prognosis ( P = 0.023, P = 0.038, respectively) in multivariable analysis with pT and pN classification [ P = 0.048; hazard ratio (HR): 2.64; 95% CI: 1.0-6.9, for EpCAM and P = 0.029; HR: 2.22; 95% CI: 1.0-4.5, for ABCG5].Poor survival time was particularly striking for lymph node-negative patients with ABCG5-positive buds ( P < 0.001).CONCLUSION: Expression of putative stem cell markers EpCAM and ABCG5 within the tumor buds of colorectal cancer are frequently noted and are associated with poor prognosis.