OBJECTIVE: To evaluate the feasibility and specimen quality of cryobiopsy for ureterorenoscopic (URS) biopsy in suspected upper tract urothelial carcinoma (UTUC). METHODS: Using a newly developed flexible cryoprobe, a total of 80 biopsies were obtained in 10 consecutive patients with renal pelvis tumors suspicious for UTUC (cryobiopsy, n = 28; forceps, n = 28; basket, n = 24). The primary endpoint was the diagnostic yield of cryobiopsy; secondary endpoints included comparison with standard instruments, feasibility, safety, and specimen quality. RESULTS: Cryobiopsy enabled a definitive histopathological diagnosis in all patients (primary endpoint). As a secondary endpoint, the percentage of diagnostic cryosamples was significantly higher than with conventional forceps (75.0% vs. 35.7%; p=0.007) or basket biopsy (29.2%; p=0.002). The proportion of representative samples was highest with cryobiopsy (82.1%) compared with forceps (46.4%, p = 0.011) and basket biopsy (54.2%, p = 0.038). Cryobiopsies were significantly larger (mean area 18.0 mm²) than forceps (6.4 mm², p<0.001) or basket specimens (9.6 mm², p=0.008). Histological assessability was highest with cryobiopsy (score 4.8 vs. 2.9 with forceps, p = 0.031, and 3.8 with basket, p > 0.999). Postoperative hematuria occurred in six of ten patients; it was managed conservatively, and no patient required transfusion or re-intervention. CONCLUSIONS: Cryobiopsy in the renal pelvis is feasible and yielded larger, higher-quality specimens than standard instruments. Whether this improves staging, risk stratification, or treatment selection requires larger multicenter trials (trial registration number DRKS00025620).