BACKGROUND: Solitary hepatocellular carcinoma (HCC) with a diameter of 3-5 cm represents a challenging clinical entity, especially for non-surgical candidates due to comorbidities. CASE: A 74-year-old man with previous history of renal cell carcinoma presented with a new incidental solitary 5 cm liver lesion on MRI. Due to his age and a high risk for post-surgical complications, after multidisciplinary tumor board review the treatment plan consisted of percutaneous thermal segmentectomy using balloon-occluded microwave ablation (b-MWA) followed by balloon-occluded transarterial chemoembolization (b-TACE) with complete tumor necrosis, as evident in subsequent follow-up imaging. This case demonstrates that b-MWA plus b-TACE could be a safe and effective combined therapy for unresectable large HCC lesions, even for those exceeding 3 cm in size. CONCLUSION: Although the presented case is anecdotal and naturally without comparisons or control, it highlights the potential value of percutaneous thermal segmentectomy with a single session combined b-MWA followed by b-TACE for the treatment of large unresectable solitary HCC lesions.

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