Despite chemotherapy, median survival of patients with advanced pancreatic cancer (APC) remains poor. Gemcitabine (GEM) remains standard treatment. Numerous phase II studies have suggested that combination therapies may improve response rates. Mitomycin C (MMC) when used as a single agent may have response rates comparable to other cytotoxic drugs. Therefore, MMC could be an interesting drug to be combined with GEM. This study aimed to assess the feasibility, toxicity and efficacy of GEM combined with MMC in patients with APC. Between April 1997 and January 2002, 55 consecutive patients were treated with GEM 800 mg/m2 i.v., days 1, 8 and 15, and MMC 8 mg/m2 i.v., day 1, every 4 weeks in an outpatient setting. Patient characteristics included: M/F 34/21, median age of 58 years, ECOG PS 0–2. A median of 3 cycles was administered. The most frequent toxicity was thrombocytopenia grade III/IV in 54% of patients. Ten patients experienced dyspnea±X-ray-proven pneumonitis (n=2). One of these patients developed a hemolytic uremic syndrome after the sixth application of MMC. There was one early death as a consequence of a stroke. The objective response rate was 29% (95% confidence interval: 17–43). Eighteen patients had stable disease resulting in an overall tumor growth control of 62%. Time to progression was 4.7 months and median overall survival was 7.25 months. We conclude that, except for thrombocytopenia, the combination of GEM and MMC is well tolerated. These results compare favorably to single-agent chemotherapy with GEM or the combination of 5-fluorouracil plus MMC. Furthermore, this regimen is cost-effective and, since it can be given on an outpatient basis, contributes to the quality of life.