A seventy-five-year-old woman with moderate chronic renal failure was admitted to evaluate a complex renal cyst in the frame of acquired cystic kidney disease. Computed tomography (CT) was performed without contrast media due to the risk of radiocontrast-induced nephrotoxicity. Sonographic investigation at our ultrasound unit revealed a hypoechoic lesion measuring 20x20 mm in size by conventional B-mode sonography, confirmed by NTHI. The Hypoechoic lesion was consistent with complex renal cyst or renal tumour. This finding triggered investigation with CEUS.A sulphur hexafluoride-filled microbubble contrast medium was injected intravenously. The focal lesion CES pattern was characterized by intralesional enhancement in the arterial phase. Further diagnostic imaging including CT with contrast media confirmed a lesion consistent with renal tumour. The patient underwent right-sided nephrectomy; histopathological work-up revealed a renal cell carcinoma. Contrast-enhanced sonography could be clinically useful for the differential diagnosis of kidney lesions in patients with chronic renal failure.