Background and AimCancer is one of the foremost causes of morbidity and mortality worldwide. Globally, colorectal cancer (CRC) is the third most diagnosed and fourth most important cause of cancer death. A total of 70% of all CRC‐related deaths occur in low‐ and middle‐income countries. In Sub‐Saharan Africa (SSA), estimating the burden of CRC is difficult. Only 27 of 43 SSA countries have formalized cancer registration systems; data quality is variable and national coverage rare.MethodsThis is a multidisciplinary, longitudinal cohort study started in January 2016. Patients >18 years with histologically confirmed primary adenocarcinoma of the colon and rectum, diagnosed within the previous 12 months, are eligible. Participants were assessed and were followed up for 3 years. Baseline information, including demographics, socioeconomic status, family history, medical and surgical non‐cancer‐related history, dietary history, colonoscopic findings, staging at presentation, treatment, and disease recurrence, is collected, as well as blood tests and histology results. Outcomes include disease recurrence (local and metastatic) and survival.Results and ConclusionThis study aims to describe the clinical presentation, management, and outcomes of adults with CRC in a multiethnic, urban South African population. It will be the first prospective study to describe clinical presentation, demographics, risk factors, treatment, and outcomes according to population group, from both private and state health‐care facilities in Johannesburg, South Africa. The results of this study will be relevant not only to South Africa but also to other SSA countries undergoing similar rates of rapid urbanization and epidemiological transition.