OBJECTIVES: To evaluate cost of colorectal cancer chemotherapies (i.e. AIO/Ardalan-regime, Mayo Clinic protocol and oral capecitabine) in different treatment settings (private office, hospital) considering recent changes in drug costs and payment mechanisms in Germany. METHODS: Resource utilization data, derived from 89 quarterly fee-listings for patients with metastatic colorectal cancer, were re-analyzed using the new EBM2000plus tariff system (introduced April 05) for office-based physicians, the 2005 DRG-System for hospital treatment and new regulation on drug prices according to the 2004 health care reform. Physician's services, drug costs, pharmacy costs and costs for implantable venous port systems and single-use pumps were considered. Several scenarios to reflect different assumptions were calculated. A third party payer perspective (statutory sickness funds) was adopted. RESULTS: Depending on the treatment setting (office-based, municipal hospital, university hospital), quarterly treatment costs for the AIO/Ardalan-regimen varied between €5412 and €15,109, and for the Mayo-Clinic protocol between €2602 and €4751. Projected costs for capecitabine were €1980. No hospitalisation was considered to be necessary for capecitabine due to its oral route of administration. Projecting these cost differences to epidemiological data and treatment pattern information results in a yearly savings potential of €117 Mio - €214 Mio (depending on assumptions on hospital care pattern) for German statutory sickness funds by switching these patients to capecitabine treatment. Compared to the original analyses, based on cost and payment mechanisms from 2000, substantial differences were observed. CONCLUSION: Treatment using the AIO/Ardalan-protocol was clearly the most expensive treatment option, treatment using capecitabine incurred lowest costs. Substantial cost-savings for sickness funds could be achieved if more patients were treated with capecitabine. Recent changes in German payment mechanisms had a substantial impact on the results of health economic evaluations.