Background and Aims: Dynamic contrast-enhanced EUS (CE-EUS) for quantification of perfusion in colonic tumors has not previously been reported in the literature. The aim of this study was to investigate correlations between perfusion parameters and vessel density assessed by immunohistochemical staining with antibodies toward CD31 and CD105. Methods: We conducted a prospective clinical study of 28 patients with left-sided colonic adenocarcinoma who underwent CE-EUS and left-sided hemicolectomy within 2 weeks. CE-EUS recordings were analyzed in 2 regions of interest: the entire tumor and the most enhanced area. Immunohistochemical staining with CD31 and CD105 was performed on tumor tissue sections. The slides were manually scanned for highly vascularized areas, and counting of vessels was performed in hotspots within the tumor and invasive front. New vasculature was assessed by CD105. Associations between CE-EUS and CD31 and CD105 were investigated using Spearman correlation. Results: We found significant P values for the correlation between CD31 and rise time (rho =.603 [95% confidence interval (95% CI),.238-.816]; P =.001) in tumor tissue and for the correlation between CD31 and rise time (rho =.50 [95% CI,.201-.695]; P =.008) and fall time (rho =.52 [95% CI,.204-.723]; P =.006) corresponding to the invasive front. We found no correlations between perfusion values evaluated by CE-EUS and CD105. Conclusions: Our results show a significant correlation for vessel density evaluated by CD31 and perfusion parameters evaluated by CE-EUS. This may be the first step toward using real-time CE-EUS for monitoring antiangiogenic therapies in colonic cancer. (Clinical trial registration number: NCT02324023.)