Two different immunohistochemical types suggestive of Large Cell Neuroendocrine (NE) carcinoma and Adenocarcinoma in a patient with known diffusely metastatic, hormone refractory prostate carcinoma are rarities. Interestingly, our patient had documented history of exposure to Agent Orange during his time of service. The use of routinely used immunohistochemical stains for pathological diagnosis was a challenge in this case, though throughout his disease course, the diagnosis was confirmed as Adenocarcinoma of prostate with biopsies from all various sites of metastases. Systemic chemotherapy has been historically suboptimal in management of aggressively behaved prostate carcinomas. Finding any association of Agent Orange as a causative etiology and improving diagnosis and management of such aggressive hormone refractory prostate carcinoma need further investigations.