Five cases of small-cell carcinoma (SCC) of prostate were identified, at the Rhode Island Hospital and the Miriam Hospital from 1984 to 2006, with an average age of 71 years at the time of diagnosis. Three of these patients had a prior diagnosis of prostatic adenocarcinoma, with all of the five patients receiving anti-androgen treatment. The average time between the diagnosis of adenocarcinoma and of SCC in these patients was 6.7 years. The PSA levels varied greatly, with two patients possessing markedly elevated levels and the remaining patients with normal levels. Approximately 3/5 patients developed liver metastases, 2/5 patients had bone metastases, and 1/5 patients developed carcinomatous meningitis. Of the four patients who expired, the median survival time after diagnosis of SCC was 3.6 months (0.5–12 months).