Keratinizing desquamative squamous metaplasia (KDSM) in the renal pelvis is a rare condition with unclear malignant potential. Recent reports suggest it is likely benign and favor endoscopic treatment approaches. Medical record review was completed on two cases at our center to obtain history, physical examination, radiographic findings, and management. A literature review was completed to identify all published cases of KDSM. Both patients at our center suffered recurrent urolithiasis, hypothesized to be secondary to KDSM. Both were managed with a percutaneous approach to ensure complete stone and KDSM plaque removal. Our cases highlight that percutaneous surgery is an excellent management option for stone and KDSM eradication from the collecting system. This approach also allows adequate oncologic surveillance of the underlying urothelium.