We present a case of a 75-year-old male with a history of high risk prostate cancer who underwent androgen deprivation therapy and palliative radiation treatments for his disease. Subsequently, he presented with gross hematuria and severe lower urinary tract symptoms. A palliative transurethral resection of the prostate (TURP) at that time, demonstrated large cell differentiated neuroendocrine carcinoma with metastasis to the lung. We review the limited literature on this rare form of disease and present current treatment strategies.