INTRODUCTION The association between staghorn calculus of the kidney long-standing and urothelial tumors of the renal pelvis is well documented. We describe 3 patients with urothelial cancer in a kidney who underwent percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS Retrospective analysis of our series of more than 500 PCNLs revealed 3 patients in whom urothelial cancer of the renal pelvis was diagnosed during or following percutaneous stone removal. Preoperative assessment included IVP, renal sonography and renal scan using DTPA in all 3 patients, and CT in 2 patients. Imaging did not raise the suspicion of a neoplastic lesion. RESULTS All patients had a long history of urolithiasis and urinary infections. No patient was diagnosed preoperatively. One patient was diagnosed postoperatively, when a CT demonstrated a renal lesion. The second patient underwent simple nephrectomy due to a non-functioning kidney, and the tumor was found on pathological analysis. In the third patient, biopsies were taken from a suspicious-looking tissue in the renal pelvis during the PCNL session. All patients had transitional cell carcinoma: 1 associated with sarcomatoid features and 1 with squamous carcinoma. They all died from metastatic disease 2-19 months after the diagnosis of urothelial cancer. CONCLUSIONS The preoperative diagnosis of urothelial cancer in patients with staghorn stones is difficult due to the existing stone and inflammation. Since the prognosis of urothelial cancer is extremely poor, biopsies of the renal pelvis, obtained directly through the nephroscope during the PCNL session, may be the only key for early diagnosis and treatment. A high index of suspicion should be raised when patients suffering from infected staghorn calculi are encountered, and such intraoperative biopsies should be considered.