Adenosquamous carcinoma of the prostate is an unusual histological variant of prostate cancer. The histogenesis of this tumor remains uncertain. The stimulus for the development of the squamous metaplastic cells had been thought to be related to hormone and/or radiation therapy. This report presents a case of adenosquamous carcinoma of the prostate with abscence of previous hormone or radiation therapy. The case showed negative prostate-specific antigen and high molecular weight cytokeratin staining of the adenocarcinoma component, and negative prostate-specific antigen and positive high molecular weight cytokeratin staining of the squamous cell carcinoma component. The adenocarcinoma component stained intraluminally with periodic acid schiff. The staining features and the distinct localizations of the components with intermingling, but no transition, are against the collision-type tumor theory and support the theory that the adenocarcinoma and squamous components arise de novo from pluripotent stem cells. The patient had a rapid downhill clinical course and died 3 weeks after the diagnosis was made.