OBJECTIVES: Metastatic colorectal cancer (mCRC) accounts for a substantial economic and clinical burden worldwide. The aim of the present study was to conduct an economic evaluation in Greece comparing panitumumab with cetuximab in the monotherapy treatment of patients with non-mutated (wild-type) KRAS, epidermal growth factor receptor (EGFR)-expressing mCRC. METHODS: Based on literature search, panitumumab and cetuximab are assumed to have similar efficacy, hence a cost-minimization analysis was carried out from the third-payer-party (Sickness Fund) and the National Health Service (NHS) perspective. A probabilistic model was constructed to estimate the resource utilization and costs associated with the management of patients receiving either therapy. Due to known differences in various settings regarding drug use, two type of analysis were undertaken: one reporting “cost per mg” and another reporting “cost per vial”. Treatment cost accounted for administration of second line chemotherapy, laboratory and biochemical examinations and for hospitalization due to toxicity. Data on resource utilization were collected from two oncology units in Greece and prices refer to 2011. Non parametric bootstrapping was employed to deal with uncertainty and to estimate variability measures.   RESULTS: From a third-payer-party perspective, it was found that the mean 20-week total cost per patient for panitumumab and cetuximab in the “per mg analysis” was €16,349 (95%CI: 16,036.7-16,637.8) and €18,242 (95%CI: 17,902.4-18,597.9), respectively. The corresponding mean total costs obtained in “per vial analysis” was €18,808 (95%CI: 18,437.7-19,161.7) and €19,701 (95%CI: 19,358.6-20,053.1), respectively. From the NHS perspective, while the mean total costs per patient were higher than for third party payers, versus cetuximab, panitumumab was still associated with a 12.40% and 17.7% cost reduction in per-vial and per-mg analysis, respectively. CONCLUSIONS: In the Greek NHS and Sickness Fund setting, panitimumab may represent a cost-saving option compared with cetuximab in the management of patients with non-mutated (wild-type) KRAS, epidermal growth factor receptor (EGFR)-expressing mCRC.