Objectives: To evaluate the histopathology of small renal tumor biopsies following cryoablation. Methods: We retrospectively evaluated small renal tumor biopsy specimens after cryoablation treatment for renal cell carcinoma and determined the ability to differentiate tumor types, effect on nuclear grading, immunohistochemical staining, and if the number of freeze cycles affected interpretation. Results: Of the biopsy specimens, 66% were diagnostic of tumor and 34% showed normal renal parenchyma. Tumor subtype was determined in 91% of diagnostic cases. Nuclear grading was affected due to freeze effect, complicating the assessment of chromatin pattern and nucleolar details at low magnification. In particular, the distinction between Fuhrman nuclear grades I and II was compromised; these were designated as low nuclear grade. Immunohistochemical staining was retained similar to untreated tumors. Tumor subtyping was not affected after one or two freeze cycles. Conclusions: Biopsies performed immediately after cryoablation can be used to render an optimal histologic diagnosis.