Background. Ubiquitin-conjugating enzyme E2T (UBE2T) is overexpressed in several types of malignancies. However, little is known about its diagnostic significance in intrahepatic cholangiocarcinoma (ICC) and other bile duct diseases or its prognostic value in ICC. Methods. The expression levels of UBE2T in the intrahepatic bile duct (IHBD, N = 13), biliary intraepithelial neoplasia (BilIN; BilIN-1/2, N = 23; BilIN-3, N = 11), and ICC (N = 401) were examined by immunohistochemistry. The differential diagnostic and prognostic values were also assessed. Results. The number of UBE2T-positive cells was significantly higher in ICC tissues than in nonmalignant tissues, including the IHBD, BilIN-1/2, and BilIN-3 tissues. Kaplan-Meier analysis showed that overexpression of UBE2T was correlated with a shorter time to recurrence (TTR) and overall survival (OS). The 5-year TTR rates in the high UBE2T and low UBE2T groups were 100% and 86.2%, respectively. The corresponding OS rates were 1.9% and 22.2%, respectively. High expression of UBE2T was an independent risk factor for both TTR (hazard ratio: 1.345; 95% confidence interval: 1.047,1.728) and OS (hazard ratio: 1.420; 95% confidence interval: 1.098,1.837). Conclusions. UBE2T can assist in differentiating benign bile duct diseases from ICC, and high expression of UBE2T suggests a poor prognosis for ICC.