Experience with carcinoma in situ (CIS) of the urinary bladder during a twenty-year period at the Mayo Clinic is reviewed. The most important clinical clues for diagnosis of this disease continue to be irritative bladder symptoms in the absence of infection in elderly men and a history of transurethral resection of the prostate. The most reliable method of diagnosis is urinary cytology. When not modified by treatment, CIS is the precursor of most invasive cancers, originating probably from an area of atypical hyperplasia into CIS and, finally, into invasion. Among patients considered to have CIS who undergo cystectomy, 34 per cent may already have microinvasion. CIS has the potential to involve the entire urothelium. Prudence should guide the use of intravesical chemotherapy (mitomycin or thiotepa or doxorubicin), which may control the disease for extended periods in many patients. If primary treatment fails, immediate second-line treatment should include BCG or hematoporphyrin derivative (HpD) phototherapy or both. If such therapy fails, delay of radical cystectomy seems inadvisable. Monitoring of the prostatic urethra during intravesical treatment is mandatory; a radical surgical procedure should be performed once the prostatic urethra is involved. Results of treatment for secondary prostatic and upper urinary tract cancer are dismal. Conversely, secondary urethral disease, although it occurs frequently beyond five years, may be associated with a good prognosis.