Post-colonoscopy colorectal cancer (PCCRC), classified as colorectal cancer (CRC) diagnosed following a negative colonoscopy and prior to the recommended follow-up; despite advancements in the quality of colonoscopy, remains a significant concern. PCCRC accounts for 1.8 to 9.0% of CRC cases globally and 6.2% CRC cases in Korea. The predominant reasons for the incidence of PCCRC include procedural factors such as missed lesions and incomplete resections, and newly developed lesions. Few strategies that can mitigate PCCRC include improving adenoma detection rates to at least 25 to 35%, ensuring withdrawal times of ≥ 8 minutes, adequate bowel preparation, and cecal intubation rates exceeding 90 to 95%. For preventing PCCRC, advanced imaging technologies and enhanced polypectomy techniques, such as en bloc resection for larger or potentially malignant polyps are critical. This review highlights the multifactorial nature of PCCRC and the significance of quality assurance in colonoscopy for reducing its prevalence.