The relationship between cyclophosphamide and hemorrhagic cystitis is well documented; its role in inducing bladder cancer is less clear. To date, 18 cases of cyclophosphamide-associated bladder tumors have been reported. We present 3 additional cases of transitional cell bladder cancer, all preceded by hemorrhagic cystitis. Data implicating cyclophosphamide as a direct carcinogen as well as an immunosuppressive agent allowing bladder tumor development in the compromised host are discussed. While no direct relationship has been established, we suggest patients receiving this drug are at risk for developing bladder cancer, more likely transitional cell rather than squamous cell as has been reported previously.