The purpose of this study was to assess the ability of pulse-inversion ultrasound (US) scanning (PIUS), combined with an IV contrast agent, to detect malignant liver lesions and its impact on patient management (resectability). Additionally, to determine the feasibility of US-guided biopsy of new PIUS-findings at the same session. A total of 30 patients with known or clinically suspected cancer underwent conventional B-mode scanning and PIUS with IV-administered contrast agent. The number of liver metastases in the right and the left liver lobe, respectively, was recorded. All patients with additional findings by PIUS underwent US-guided biopsy. PIUS provided additional information in 18 patients (60%); of these, 13 (43%) had additional metastases. Of 19 patients found resectable by conventional US, 9 (47%) were considered inoperable using PIUS supported by biopsies. Biopsies of additional findings were performed in 17 of 18 patients. All biopsies of additional findings confirmed malignancy. PIUS with an IV contrast agent increased the ability to detect liver metastases compared to conventional US scanning. The technique had a high impact on patient management. The results showed that PIUS-guided biopsy was possible. PIUS with IV contrast will undoubtedly become an important diagnostic tool in the evaluation of patients with metastatic liver disease.