We report two cases of combined small-cell carcinoma (SCC) and adenocarcinoma of prostate. Case 1 was a 76-year-old man with loss of appetite and body weight and neck lymphadenopathies. Whole body computed tomography (CT) revealed prostatic swelling, pancreatic mass, para-aortic lymphadenopathies, and multiple lung nodules. Elevation of tumor markers (prostate specific antigen [PSA, 1,760 ng/ml] and neuron-specific enolase [NSE, 88 ng/ml]) was noted. Needle biopsy of the prostate demonstrated both SCC and adenocarcinoma. Only within the part of SCC, were neuroendocrine (NE) markers (chromogranin A [CgA], NCAM, and synaptophysin [SNP]) expressed. Maximum androgen blockade (MAB) resulted in a decrease of PSA (5.13 ng/ml) but an increase of NSE (810 ng/ml). Cytotoxic chemotherapy was not possible because of his poor performance state and renal dysfunction. The patient died three months after the diagnosis. Case 2 was a 69-year-old male with dysuria. The symptom and elevated serum PSA (23.1 ng/ml) prompted prostatic needle biopsy, which demonstrated combined SCC/adenocarcinoma. NE markers (CgA and SNP) were weakly expressed in the part of SCC. Serum NSE was 6.9 ng/ml. After MAB, serum PSA dropped to the normal range (0.192 ng/ml) and the effect of MAB was judged as complete response (CR). The patient has been alive for 15 months with no signs of relapse. Treatment of combined SCC and adenocarcinoma of prostate poses a dilemma. In Case 1, MAB was effective for adenocarcinoma but not for SCC. The opposite situation would be expected with systemic chemotherapy. However, the histologically similar Case 2 achieved CR with MAB alone. Much remains to be elucidated to better manage combined SCC/adenocarcinoma of prostate.