Colorectal adenocarcinoma (CRC), the second leading cancer-related death in the United States, remains a global public health issue. Sporadic CRC is considered the result of sequential mucosal changes from normal colonic mucosa to adenocarcinoma. Efforts in understanding the molecular pathways leading to CRC tumorigenesis may lead to identifying novel, individually tailored therapeutic targets for patients. In this review, we focus on well-published prognostic and predictive markers in CRC and examine their role in clinical practice. J. Surg. Oncol. 2015 111:96–102. © 2014 Wiley Periodicals, Inc.