Cetuximab was approved using a weekly schedule, alone or in combination with chemotherapy (CT). However, many CT regimens in metastatic colorectal cancer (CRC) are delivered every 2 weeks (q2wks). Preliminary data suggested that a simplified schedule using cetuximab q2wks, 500 mg/m² would be equivalent to the standard weekly administration. Medical data of all patients with advanced CRC who received cetuximab q2wks were retrospectively collected and checked for consistency by an independent monitor in 4 European centers. Ninety-one patients were treated between 2005 and 2007 when the K-RAS mutational status of tumors was not determined routinely. They received a median of 4 (0-5) previous drugs, including previous weekly cetuximab in 38.5% of patients. Cetuximab q2wks was associated with an irinotecan-based regimen in 85.7% of patients. The median number of cetuximab administrations was 6 (1-23). Skin toxicity was observed in 68.2% of evaluable patients (grade 3 in 15%). Only one grade 1 allergy was reported. In the 84 patients beyond first-line therapy, response rate was 29.3%. The median progression-free survival was 3.0 months (range 2.2-3.8), and median overall survival was 9.0 months (range 6.2-11.8). Cetuximab q2wks appears safe and effective in heavily pretreated patients and convenient in combination with q2wks CT schedules.