Ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate with a poorly understood natural history, and its treatment is not well defined. Ductal adenocarcinoma is often diagnosed at an advanced stage, because no specific tumor markers are known. Docetaxel has been used for acinar adenocarcinoma of the prostate, a common type of prostate cancer, but it is largely ineffective for ductal adenocarcinoma. Earlier studies suggested that the chemotherapy with gemcitabine and cisplatin might be effective for ductal adenocarcinoma. Here we report two patients with ductal adenocarcinoma of the prostate that did not respond to docetaxel, but responded to the gemcitabine/cisplatin chemotherapy. Patient 1 was a 59-year-old man who had lung metastasis despite androgen deprivation therapy with undetectable levels of prostate-specific antigen and who presented with brain metastasis during docetaxel chemotherapy. Pathological examination of the resected brain tumor revealed ductal adenocarcinoma with positive immunostaining for carcinoembryonic antigen. The gemcitabine/cisplatin chemotherapy achieved partial response of the lung metastasis with serum carcinoembryonic antigen levels decreasing from 11.4 ng/mL to 2.9 ng/mL. Patient 2 was a 69-year-old man with lung metastasis. Local progression appeared during androgen deprivation therapy, and the subsequent transurethral biopsy revealed ductal adenocarcinoma with positive immunostaining for neuron-specific enolase. Bone and distant lymph node metastasis appeared despite docetaxel chemotherapy. Six courses of the gemcitabine/cisplatin chemotherapy achieved partial response of metastatic lesions, with serum neuron-specific enolase levels decreasing from 118 ng/mL to 2.6 ng/mL. The gemcitabine/cisplatin chemotherapy is a potential option for treatment of advanced ductal adenocarcinoma of the prostate.