Prostatic adenocarcinoma rarely may involve the urinary bladder. Prostatic adenocarcinoma and high-grade transitional cell carcinoma (TCC) may coexist and account for the malignant cells seen in urinary cytology. Differentiating prostatic adenocarcinoma cells from those of TCC is important for therapy but remains difficult. A 10-year retrospective search identified 250 patients with high-grade carcinoma in urinary cytology. Among them, 6 cases of tissue-documented prostate adenocarcinoma were identified. The cytologic features of these cases were compared with those of 15 similarly documented cases of high-grade TCC. By using these criteria, 2 additional cases of prostatic adenocarcinoma were diagnosed prospectively. An oval nucleus with smooth borders; fine, powdery, evenly distributed nuclear chromatin and a large prominent nucleolus when present; and lack of significant pleomorphism are most helpful to differentiate prostatic adenocarcinoma from high-grade TCC. Recognizing these cells may be the first clue for the diagnosis of prostate adenocarcinoma.