Iatrogenic immunosuppression following renal transplantation has been associated with the development and progression of multiple neoplasms, including transitional cell carcinoma (TCC). We present the first report of invasive TCC of the bladder managed with radical cystectomy in a cardiac transplant recipient. The short survival of this patient, despite organ-confined disease at the time of cystectomy, illustrates the necessity of early diagnosis and aggressive treatment of malignancy following organ transplantation.