Colorectal cancer is less common in the Middle East and South Asia than in western countries, with the rectum the most common primary site, unlike in the United States. A project was planned to address various local issues regarding the management of common cancers, including colorectal cancer, and to adapt the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to the Middle East and North Africa (MENA) region. A survey of oncologists in this geographic area showed that the management practices and issues regarding colorectal cancer are similar to those presented in the NCCN Colorectal Cancer Guidelines. However, 2 major differences exist: most oncologists in the MENA region prefer chest radiograph over CT in pretreatment workup, and almost 50% of them prefer to use cetuximab in the first-line treatment of patients with the wild-type KRAS gene. The committee, comprising 9 oncologists from different countries, proposed 4 modifications to the 2009 version of the NCCN Colorectal Cancer Guidelines for use in the MENA region, relating to 1) short-course preoperative radiotherapy, 2) dose of capecitabine, 3) stereotactic radiotherapy for liver metastasis, and 4) qualification of surgeons performing colorectal surgery. The modification of NCCN Colorectal Cancer Guidelines for use in the MENA region represents a step toward creating a uniform practice in the region based on evidence and local experience.