Objective: We estimated the total medical costs incurred during the 5 years following a cancer diagnosis and annual medical use status for the six most prevalent cancers in Korea. Methods: From January 1 to December 31, 2006, new patients registered with the six most prevalent cancers (stomach, liver, lung, breast, colon, and thyroid) were randomly selected from the Korea Central Cancer Registry, with 30% of patients being drawn from each cancer group. For the selected patients, cost data were generated using National Health Insurance claims data from the time of cancer diagnosis in 2006 to December 31, 2010. The total number of patients selected was 28,509. Five-year total medical costs by tumor site and Surveillance, Epidemiology, and End Results (SEER) stage at the time of diagnosis, and annual total medical costs from diagnosis, were estimated. All costs were calculated as per-patient net costs. Results: Mean 5-year net costs per patient varied widely, from $5,647 for thyroid cancer to $20,217 for lung cancer. Advanced stage at diagnosis was associated with a 1.8-2.5-fold higher total cost, and the total medical cost was highest during the first year following diagnosis and decreased by the third or fourth year. Conclusions: The costs of cancer care were substantial and varied by tumor site, annual phase, and stage at diagnosis. This indicates the need for increased prevention, earlier diagnosis, and new therapies that may assist in reducing medical costs.