OBJECTIVES: This study aimed to evaluate the cost-effectiveness of percutaneous renal mass biopsy (RMB) in the management of small renal masses (SRMs). METHODS: A Markov model was developed to compare the lifetime costs and quality-adjusted life years (QALYs) of RMB with possible delayed treatment and immediate treatment from the societal perspective in a hypothetical cohort of 65-year-old healthy patients with asymptomatic unilateral SRMs. The treatments included percutaneous ablation (PA), laparoscopic ablation (LA), robotic partial nephrectomy, open partial nephrectomy (OPN), laparoscopic radical nephrectomy, and open radical nephrectomy. The willingness-to-pay threshold was $50,000/QALY-gained. Robustness of the model was assessed using sensitivity analyses. RESULTS: Among all the options, RMB with possible PA had the lowest total costs and QALYs. RMB with possible OPN was the optimal choice compared with RMB with possible PA (incremental cost-effectiveness ratio: $6,397/QALY-gained). In pairwise comparisons, RMB was preferred to the corresponding immediate treatment. If chronic kidney disease (CKD)-incurred costs were above the treatment-specific threshold, RMB was preferred. RMB with possible LA or partial nephrectomy was favored over the immediate treatment in old patients. RMB with possible radical nephrectomy was preferred to the immediate treatment regardless of age at diagnosis, tumor size and comorbidities. However, immediate PA was preferred to RMB in old patients with a large tumor. CONCLUSIONS: RMB with possible OPN was the optimal strategy. Among pairwise comparisons, RMB was preferred to immediate treatment. The results were sensitive to CKD-incurred costs, age and tumor size.