There is a continuous increase in incidentally diagnosed small renal masses, with a predominant rise in the elderly and frail population, making less invasive energy ablative therapy strategies more desirable. The decision for treatment and follow-up strategies, however, are commonly based on sequential radiologic CT or MRI investigations only. In small renal masses, up to 30% benign tumors may be found, not necessitating any treatment. Likewise, all currently available energy ablative techniques must be compared with respect to safety and efficacy; this is only possible by histologic definition of the treated target. Finally, not only for academic reasons, the malignant entity of the treated mass must be known for further follow-up investigations, especially when insufficient ablation is suggested during follow-up-suggested by lack of shrinkage and persisting contrast enhancement on CT or MRI. Therefore, liberal use of renal mass biopsy (Bx) is mandatory before any focal therapy. There is some role for intraoperative biopsy in selected cases and for study purposes. Conversely, the role of postfocal therapy Bx protocols remains unclear but seems at least mandatory in lesions that are seemingly insufficiently treated during follow-up. This article gives an overview of Bx protocols suggested in the literature and obtained by personal experience in the continuous use of several energy ablative techniques.