Urinary calculi can induce urothelial cellular abnormalities comparable with those of malignancy; this was found in 11 out of 62 lithiasis cases. Severe cellular changes, comparable with those of carcinoma in situ, may be seen in the epithelium adjacent to a calculus. Squamous metaplasia was frequently observed in cases with staghorn stones in the renal pelvis. The abrasive effect of the calculus may result in many multinucleated cells in the sediment. When the calculi are removed the cytological atypia and the observed multinucleation disappeared, and none of these 62 patients developed urothelial carcinoma. A possible relationship was found between a long-term clinical history of lithiasis and the development of cancer of the upper urinary tract in a study of 92 cases of carcinoma of the ureter and renal pelvis.