The aim of the present study was to examine the epidemiology, natural history, treatment and long-term survival of patients with adenosquamous cell carcinoma of the prostate. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify ASCC of prostate cases between January 1973 and December 2006. Survival probabilities were estimated using the Kaplan-Meier methods and compared using the log-rank test. A total of 25 patients with adenosquamous cell carcinoma of the prostate were identified during the study period. The median age was 74 years (range 53-98). Twenty percent of study subjects presented with metastatic disease. Among those patients with known grade (n=16), 75% had poorly or undifferentiated histology. A total of 40% of study subjects received radical prostatectomy, while 24% of the patients had primary radiation therapy. The 1-, 3-, and 5-year cancer specific survival rates for the entire cohort were 55.2%, 37.8%, and 30.3%, respectively. For patients who underwent prostatectomy, the 1-, 3-, and 5-year survival rates were 78%, 78%, and 63%, respectively. For the patients who did not receive prostatectomy, the 1-year survival rates were 38.7% and none survived to three years. Adenosquamous cell carcinoma is a rare aggressive subtype of prostate cancer with poor cancer specific survival. The development of new therapeutic approaches for this aggressive tumor is urgently needed.