The female urethra is lined by transitional cell mucosa proximally and stratified squamous cells distally. Therefore, transitional cell carcinoma is most common in the proximal urethra and squamous cell carcinoma predominates in the distal urethra. Adenocarcinoma is found in both locations and arises from metaplasia of the numerous periurethral glands.

The male urethra is lined by transitional cells in its prostatic and membranous portion and stratified columnar epithelium to stratified squamous epithelium in the bulbous and penile portions. The submucosa of the urethra contains numerous glands. Therefore, urethral cancer in the male can manifest the histological characteristics of transitional cell carcinoma, squamous cell carcinoma, or adenocarcinoma.

Except for the prostatic urethra, where transitional cell carcinoma is most common, squamous cell carcinoma is the predominant histology of urethral neoplasms. Since transitional cell carcinoma of the prostatic urethra is usually associated with transitional cell carcinoma of the bladder and/or transitional cell carcinoma arising in prostatic ducts, it is treated according to the guidelines for treatment of these primaries and should be separated from the more distal carcinomas of the urethra.

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