We report a rare case of squamous cell carcinoma developing in a defunctionalized bladder with known leukoplakia 19 years after urinary diversion. We conclude from this case that once the initial metaplasia of the transitional epithelium of the urinary tract to leukoplakia has occurred chronic irritation by (infected) urine is not required to cause further progression to squamous cell carcinoma. Therefore, we recommend prophylactic cystectomy if palliative urinary diversion for relief of symptoms is considered in patients with leukoplakia of the bladder.