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CEUS has increased the capability of ultrasonography for the detection of focal liver lesions (FLL). The differential diagnosis between hepatocellular carcinoma (HCC) and other malignant tumors may be limited by similarities in the appearance of CEUS. The aim of this study was to evaluate the role of combination of LR-4 and LR-5 by adding ancillary features (AFs) in the CEUS LI-RADS v2017 algorithm for the diagnosis of definite HCC. This retrospective single- center study included 143 patients with 191 FLL detected by abdominal ultrasound from a total of 823 consecutive patients. The risk factors were liver cirrhosis of any etiology and non-cirrhotic HBV patients. Diagnosis was established either through histopathology or based on CT/MRI scan. CEUS recordings were assessed by an EFSUMB level 3 sonographer, with more than 10 years experience in CEUS and who was blinded to clinical data and to the final diagnosis. All lesions have been categorized according to the CEUS LI-RADS® described by The American College of Radiology scheme. The AFs were taken into account. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated. PPV for primitive malignancy (LR-4 + LR-5) was 95.7% (95CI%: 90.7–98%), with 88.07% sensitivity, 89.3% specificity and 88.4% accuracy for HCC (95CI%: 82.8–92.6%). LR4 + LR5 had 81.8% sensitivity for HCCs over 2 cm (n = 127), and 78.57% sensitivity for HCCs less than 2 cm (n = 14). Both sensitivity and accuracy of LR-4 + LR-5 for the diagnosis of definite HCC considerably raised to 88.07% and 88.4%, unlike the sensitivity and accuracy for LR-5 of only 60.45% and 69%, respectively. NPV also improved (73.4% vs. 46.6%), while similar high PPVs (95.7% vs. 96.2%) and quite similar specificity (89.3% vs. 93.6%) were maintained. Higher sensitivity than estimated for the diagnosis of HCCs smaller than 2 cm was achieved for CEUS LR-4 and LR-5. The use of AFs might improve the overarching goal of CEUS LR-5 + LR-4 diagnosis of high specificity for HCC and exclusion of non-HCC malignancy, despite the size of the lesion. [ABSTRACT FROM AUTHOR]