CT may miss up to 30% of cases of colorectal liver metastases (CRLM). We assessed the impact of contrast-enhanced ultrasound (CEUS) on the detection of CRLM and changes to the therapeutic strategy, and the accuracy of CEUS in differentiating unclear focal liver lesions (FLL) compared to staging-CT.We prospectively analyzed all patients with newly diagnosed and histologically confirmed colorectal cancer (CRC) at our tertiary gastroenterological center between December 2015 and May 2019. CEUS was performed in a total of 296 patients without CRLM after staging-CT using the contrast agent (SonoVue®). Standard of reference was obtained by MRI or histology to diagnose CRLM missed by CT. Benign FLL were confirmed by MRI or follow-up CT (mean follow-up interval: 18 months).Eight additional CRLM were detected by CEUS (overall 2.7%; sensitivity 88.9%, specificity 99.0%, positive predictive value 100%, negative predictive value 99.6%). All patients with CRLM detected only by CEUS were in tumor stage T3/T4 (4.0% additionally detected CRLM). The number needed to screen to detect one additional CRLM by CEUS was 37 in all patients and 24.5 in T3/T4-patients. When results were reviewed by a board-certified radiologist and oncologist, the therapeutic strategy changed in 6 of these 8 patients. Among the 62 patients (20.9%) with unclear FLL after staging-CT, CEUS determined the dignity of 98.4% of the FLL.CEUS detected overall 2.7% additional CRLM (including 4.0% in tumor stage T3/T4) with a significant impact on the oncological therapeutic strategy for 75% of these patients. Patients with tumor stage T3/T4 would particularly benefit from CEUS. We propose CEUS as the first imaging modality for CT-detected lesions of unknown dignity.