Background/Aim: The challenges of cololorectal cancer (CRC) management include prediction of outcome and drug response or chemoresistance. This study aimed at examining whether beta III-tubulin (TUBB3), present in various types of normal tissues and cancer, is a biomarker for the response of colorectal neoplasms to paclitaxel. Materials and Methods: Six tissue microarrays (TMAs) including 14 colon mucosa, 78 polyps and 202 CRCs were constructed. Assessment of TUBB3 expression was performed by immunohistochemistry, and it was scored as negative, focal and positive. In the HCT116 cell line, TUBB3 expression was silenced with siRNA. Paclitaxel toxicity was evaluated in TUBB3-silenced and control HCT116 cell lines. Results: The non-neoplastic colon mucosa was negative for TUBB3, while some of colon adenomas and CRCs expressed TUBB3 in various levels from focal to diffuse. TUBB3-expressing CRCs tended to have poor prognosis and silencing of TUBB3 sensitized the cells to paclitaxel. Conclusion: TUBB3 was expressed in a subgroup of colorectal neoplasms. Suppression of TUBB3 potentialy sensitizes neoplastic cells to taxanes.