Background <p>Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cystic enlargement and an increased risk of renal cell carcinoma. Early diagnosis and treatment are often hindered by severe distortion of renal architecture and by the limitations of contrast-enhanced computed tomography or magnetic resonance imaging in patients with impaired renal function. Contrast-enhanced ultrasound offers a nephrotoxic-free alternative for lesion characterization, treatment planning, and post-ablation monitoring.</p> Case presentation <p>A 44-year-old woman was referred for evaluation of newly detected autosomal dominant polycystic kidney disease (ADPKD). Admission ultrasound showed markedly enlarged cystic kidneys and a 2.2-cm isoechoic lesion in the left kidney that could not be characterized due to the distorted anatomy. To avoid repeat contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI), contrast-enhanced ultrasound demonstrated heterogeneous intralesional enhancement with relatively rapid washout, and positron emission tomography-computed tomography (PET-CT) showed focal hypermetabolism. After cessation of dual antiplatelet therapy and correction of anemia, ultrasound-guided core biopsy confirmed renal cell carcinoma. The patient underwent percutaneous radiofrequency ablation, and post-procedural contrast-enhanced ultrasound (CEUS) showed no residual enhancement. Follow-up imaging at 6 and 24 months revealed no recurrence, and renal function remained stable.</p> Conclusions <p>This case highlights the role of CEUS in detecting and characterizing renal tumors in ADPKD, and its utility in post-ablation surveillance. Ultrasound-guided radiofrequency ablation (RFA) is a safe, nephron-sparing treatment for localized RCC in ADPKD patients, especially when traditional contrast-enhanced imaging is limited by renal dysfunction.</p>