Colorectal cancer (CRC) has become a major cause of cancer-related mortality in Western countries, accounting for about 10% of such deaths. This increase is attributed to an aging population, poor dietary habits, and other risk factors like smoking and obesity. While new treatments for CRC have been developed, they have not significantly improved cure rates or long-term survival. Screening programs have gained momentum due to the long preclinical phase of CRC, which allows for early detection. This Primer provides an overview of current knowledge on the epidemiology, mechanisms, diagnosis, and treatment of CRC. CRC is the second- and third-most common cancer in women and men, respectively. In 2012, over 1.3 million cases were diagnosed globally. The incidence varies geographically, with higher rates in developed regions and lower rates in less developed regions. The age-standardized incidence rate is higher in men than in women. CRC is associated with various risk factors, including genetic and environmental factors. Genetic factors include hereditary syndromes like Lynch syndrome and familial adenomatous polyposis, while environmental factors include lifestyle choices such as smoking, alcohol consumption, and diet. The mechanisms of CRC involve the accumulation of genetic and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. The progression of CRC typically follows a predictable sequence from benign polyps to cancer. Different molecular subtypes of CRC exist, each with distinct genetic and epigenetic features. These subtypes include hypermutable/microsatellite unstable (Hyp-MSI), hypermutable-microsatellite stable (Hyp-MSS), microsatellite stable (MSS), and CIMP cancers. Diagnosis of CRC can be achieved through various methods, including colonoscopy, which is the gold standard. Other methods such as chromoendoscopy, narrow band imaging, and capsule endoscopy are also used. Screening programs are crucial for early detection and prevention of CRC. These programs aim to detect precancerous lesions and reduce the incidence and mortality of CRC. The effectiveness of screening is influenced by factors such as the quality of the procedure, the accuracy of the test, and the uptake of screening programs. The role of the gut microbiota in CRC is also being investigated. Certain bacteria, such as Fusobacteria, have been associated with CRC, particularly in cancers with CIMP status. The use of biomarkers, such as SEPT9 methylation, is being explored for non-invasive screening of CRC. However, these tests have limitations in detecting all types of CRC. Surveillance after resection is important for patients who have had adenomatous polyps or CRC, as they remain at risk for new lesions. Guidelines for surveillance vary, but generally recommend regular follow-up based on the findings of the initial examination. The effectiveness of screening programs is influenced by factors such as the quality of the procedure, the accuracy of the test, and the uptake ofColorectal cancer (CRC) has become a major cause of cancer-related mortality in Western countries, accounting for about 10% of such deaths. This increase is attributed to an aging population, poor dietary habits, and other risk factors like smoking and obesity. While new treatments for CRC have been developed, they have not significantly improved cure rates or long-term survival. Screening programs have gained momentum due to the long preclinical phase of CRC, which allows for early detection. This Primer provides an overview of current knowledge on the epidemiology, mechanisms, diagnosis, and treatment of CRC. CRC is the second- and third-most common cancer in women and men, respectively. In 2012, over 1.3 million cases were diagnosed globally. The incidence varies geographically, with higher rates in developed regions and lower rates in less developed regions. The age-standardized incidence rate is higher in men than in women. CRC is associated with various risk factors, including genetic and environmental factors. Genetic factors include hereditary syndromes like Lynch syndrome and familial adenomatous polyposis, while environmental factors include lifestyle choices such as smoking, alcohol consumption, and diet. The mechanisms of CRC involve the accumulation of genetic and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. The progression of CRC typically follows a predictable sequence from benign polyps to cancer. Different molecular subtypes of CRC exist, each with distinct genetic and epigenetic features. These subtypes include hypermutable/microsatellite unstable (Hyp-MSI), hypermutable-microsatellite stable (Hyp-MSS), microsatellite stable (MSS), and CIMP cancers. Diagnosis of CRC can be achieved through various methods, including colonoscopy, which is the gold standard. Other methods such as chromoendoscopy, narrow band imaging, and capsule endoscopy are also used. Screening programs are crucial for early detection and prevention of CRC. These programs aim to detect precancerous lesions and reduce the incidence and mortality of CRC. The effectiveness of screening is influenced by factors such as the quality of the procedure, the accuracy of the test, and the uptake of screening programs. The role of the gut microbiota in CRC is also being investigated. Certain bacteria, such as Fusobacteria, have been associated with CRC, particularly in cancers with CIMP status. The use of biomarkers, such as SEPT9 methylation, is being explored for non-invasive screening of CRC. However, these tests have limitations in detecting all types of CRC. Surveillance after resection is important for patients who have had adenomatous polyps or CRC, as they remain at risk for new lesions. Guidelines for surveillance vary, but generally recommend regular follow-up based on the findings of the initial examination. The effectiveness of screening programs is influenced by factors such as the quality of the procedure, the accuracy of the test, and the uptake of