Background and purposeMerkel cell carcinoma is a rare and aggressive primary cutaneous neuroendocrine carcinoma with a high risk of loco-regional and distant metastasis. It is predominantly seen in the elderly, on the head and neck or extremities. Although treated primarily with surgery, some patients are too frail. A World Health Organization performance status of two or more with co-existing medical co-morbidities, or the site of the disease adjacent to a critical structure, can prevent surgical management. In this cohort of patients, primary palliative radiotherapy has been found to achieve excellent tumour regression and improve quality of life. A new palliative split-course hypofractionated regime has been used in North Middlesex University Hospital in this cohort of patients. The purpose of this case series was to provide supporting evidence on the efficacy of this dose and fractionation regime and review the literature for the palliative management of Merkel cell carcinoma.Materials and methodsIn total, four patients were treated with the palliative split-course hypofractionated regime. The regime consisted of an initial 20 Gray in 5 fractions over 1 week, a 2-week gap and then a further 20 Gray in 5 fractions over 1 week. Tolerability and response to treatment were evaluated by history and clinical examination.Results and conclusionThe split-course hypofractionated regime was well tolerated, achieved excellent tumour regression and improved quality of life in all four patients. Since then, a further three patients have been successfully treated with the above regime. This case series demonstrates the efficacy of this dose and fractionation in a select group of patients too frail for radical management and adds to the evidence base for the optimal palliative management of Merkel cell carcinoma.