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(1) Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer of neuroendocrine origin generally seen in patients over 50 years of age. It has a high propensity for recurrence post-treatment; 5-year overall survival rates range from 23% to 80%. (2) The rarity of MCC means that there is a lack of prospective controlled trials in these patients. Patients are generally treated with surgery as a first-line therapy, supplemented with adjuvant radiotherapy and chemotherapy if required. (3) The use of adjuvant therapies in MCC remains controversial. Data from case series and meta-analyses of case series suggest that the addition of radiotherapy to surgery in patients with MCC can confer significant benefits with regard to reducing local and regional recurrence rates and prolonging disease-free survival. Generally, the current literature tends not to support the use of chemotherapy in these patients. (4) Stage-specific treatment regimens have been outlined involving various combinations of surgery, radiation and chemotherapy for International Union Against Cancer (UICC) stage I to III disease, while the emphasis of treatment in patients with UICC stage IV disease is on palliative care with or without radio- or chemotherapy. There is a need for more structured clinical research to better illuminate the most effective treatments for this disease.