Background and Purpose: Keratinizing desquamative squamous metaplasia (KDSM) of the upper urinary tract is a rare condition for which there is no defined management plan. A condition historically treated with extirpative surgery, conservative management would be preferable, because this is almost certainly a benign condition. We report the favorable clinical course of two cases of renal KDSM diagnosed and managed with a nephron-sparing approach, relying on ureteroscopy and serial imaging. Patients and Methods: Retrospective chart review was performed to obtain history, physical examination results, radiographic imaging, and diagnostic procedures. Results: Both patients were referred to our institution for evaluation of complex cystic renal masses. Both reported passing flaky material in their urine. Flexible ureteroscopy revealed waxy sediment in the collecting system, which broke up easily with manipulation and proved to be squamous keratin debris on cytologic and histologic examination. In 1 patient, we obtained a percutaneous needle biopsy as well, which revealed benign keratinizing squamous epithelium. All findings were consistent with KDSM. Each patient has since been followed conservatively with CT. In 1 case, there has been slight growth of the mass but no worrisome changes after 42 months. In the other case, there were several new renal collecting system filling defects on CT 17 months after diagnosis. Another ureteroscopy revealed the same findings as the original, with the addition of keratin debris draining out of the lesion into the rest of the kidney. Conclusions: Our two cases of KDSM confirm the feasibility of nephron-sparing management using a combination of diagnostic ureteroscopy and imaging surveillance. The duration of follow-up without adverse events suggests that the finding of renal KDSM is not necessarily an indication for extirpative surgery, and that conservative management is an appropriate option.