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Background: Fatty liver disease became the most prevalent hepatic disease worldwide. The differential diagnosis of focal fatty lesions (FFL) may be challenging in clinical practice. To establish the role of contrast-enhanced ultrasound (CEUS) in focal fatty lesions (FFL) characterization in metabolic associated fatty liver disease (MAFLD) vs non-alcoholic fatty liver disease (NAFLD) patients. The retrospective study was conducted over a period of 5 years. It has included patients with hepatic steatosis and FFL (focal fat deposition and focal fatty sparing) diagnosed on B-mode ultrasound. CEUS was performed in all patients. The contrast vascular pattern of focal liver lesions was followed, according to the EFSUMB guidelines. The focal fatty alterations were considered when the same enhancement pattern as the surrounding liver parenchyma was noticed. In all cases, the final diagnostic was confirmed by computed tomography (CT) or magnetic resonance imaging (MRI). Patients were included in two groups according to the presence/absences of obesity, type 2 diabetes mellitus, and metabolic disturbances: MAFLD group vs NAFLD group. 47 patients (28 women and 19 men, mean age 53 years) were enrolled. According to the biological parameters and anamnesis 30 patients were in MAFLD and 17 in the NAFLD group. The CEUS results were: 39 nodules were diagnosed with FFL, 2 with hepatocarcinoma, 2 with metastasis, 3 hemangiomas, and 1 focal nodular hyperplasia. The final diagnosis (after CT/MRI) was FFL in 37 patients, hepatocarcinoma in 4 patients, metastasis in 2 patients, hemangioma in 2 patients, and focal nodular hyperplasia in 2 patients. The performance of CEUS correct diagnosis of focal steatosis was 94.88% (100% in the MASH group and 93.34% in the NASH group). The most misdiagnosed focal lesions in steatosis patients were hepatocarcinoma and hemangioma. CEUS is a good method for focal fatty liver lesions characterization in patients with hepatic steatosis. A focal liver lesion in patients with steatosis is more probable to be FFL in MAFLD compared with NAFLD patients. [ABSTRACT FROM AUTHOR]