Introduction: Biopsy of the upper tract urothelial carcinoma (UTUC) often provides low-quality or non-diagnostic material. Cryobiopsy may improve the quality of UTUC samples. Our aim was to assess the feasibility of Material and methods: Cryobiopsies were performed using the ERBECRYO® device and ø 1.1 mm flexible cryoprobes. Adult patients with UTUC/BC undergoing diagnostic/therapeutic endoscopic procedures were included. The cryoprobes were introduced in the proximity of the tumors and activated. The tissue samples were avulsed from the tumor, extracted and placed in a fixative. Results: Six males were included. Out of these, 4 had UTUC, while 2 had BC. The median age was 68 years. Transurethral procedures were performed in 4 patients, percutaneous in 1 and combined in 1. Cryobiopsies were conducted using cystoscopes (n = 2), rigid ureterorenoscopes (n = 2), nephroscopes (n = 1) and without endoscope, through the ureteral access sheath (n = 1). Mean obtained sample size was 6.2 × 4.7 × 3.0 mm. All the specimens allowed for a histopathologic evaluation; no crushing artifacts were reported, lamina propria was present in 4 specimens, and muscularis propria was present in 1. Bleeding from the sample bed was subjectively significantly less intense than after conventional biopsies, and the procedure was found to be less challenging than standard methods. Conclusions: Cryobiopsy represents a promising advancement in the endoscopic diagnosis of UTUC. Our pilot study demonstrates its feasibility in human