There is no established or effective standard therapy for metastatic biliary tract cancer, resulting in poor prognosis. Recently, we performed combination chemotherapy of irinotecan and low-dose cisplatin (I/low-P) for three consecutive patients with metastatic biliary tract cancer. The regimen of I/low-P therapy consisted of irinotecan (60 mg/m(2)) and low-dose cisplatin (6 mg/m(2)), administered by intravenous infusion weekly or biweekly. Of the three patients, two showed a partial response, with durations of more than 20 months, and 2 months, respectively, while the third patient had stable disease for 3 months. One patient, who had jaundice, had grade 3 thrombocytopenia, but the other patients did not have any severe toxicities. Survival times were more than 20 months, 10 months, and 13 months, respectively. These outcomes suggest that I/low-P therapy is safe and may be worth trying as a first-line chemotherapy for patients with metastatic biliary tract cancer.