Estimates of the costs associated with cancer care are essential both for assessing burden of disease at the population level and for conducting economic evaluations of interventions to prevent, detect, or treat cancer. Comparisons of cancer costs between health systems and across countries can improve understanding of the economic consequences of different health-care policies and programs. We conducted a structured review of the published literature on colorectal cancer (CRC) costs, including direct medical, direct nonmedical (ie, patient and caregiver time, travel), and productivity losses. We used MEDLINE to identify English language articles published between 2000 and 2010 and found 55 studies. The majority were conducted in the United States (52.7%), followed by France (12.7%), Canada (10.9%), the United Kingdom (9.1%), and other countries (9.1%). Almost 90% of studies estimated direct medical costs, but few studies estimated patient or caregiver time costs or productivity losses associated with CRC. Within a country, we found significant heterogeneity across the studies in populations examined, health-care delivery settings, methods for identifying incident and prevalent patients, types of medical services included, and analyses. Consequently, findings from studies with seemingly the same objective (eg, costs of chemotherapy in year following CRC diagnosis) are difficult to compare. Across countries, aggregate and patient-level estimates vary in so many respects that they are almost impossible to compare. Our findings suggest that valid cost comparisons should be based on studies with explicit standardization of populations, services, measures of costs, and methods with the goal of comparability within or between health systems or countries. Expected increases in CRC prevalence and costs in the future highlight the importance of such studies for informing health-care policy and program planning.