Colorectal cancer (CRC) develops from a dysplastic precursor lesion, regardless of whether it arises sporadically, in the setting of high-risk hereditary conditions, or in the context of chronic inflammation like inflammatory bowel disease (IBD). This review focuses on the molecular alterations associated with CRC pathogenesis in IBD. Although none of the molecular alterations to be discussed have yet been integrated into clinical practice, there is potential for molecular diagnostics to enhance the management of patients with long-standing IBD.