Merkel cell carcinoma (MCC) is an aggressive, rare tumour of the skin. For advanced cases with distant organ metastases several different regimens of chemotherapeutics have been described. Disease specific 5-year survival rates for these patients are approximately 11%. In this case series we report our experience with orally administered etoposide (100 mg at days 1 to 10 in a 31 day cycle) in 4 patients. We treated two male and two female patients with a median age of 68.5 years. In our four treated patients the disease control rate (complete remission, partial remission, stable disease) was 100%. Three out of four patients reached complete remission. Promisingly, two of our patients had long lasting, durable responses which, until now, have lasted for 16 and 36 months, respectively. The mean follow up time after start of therapy was 14.25 months (range 1-36 months). Etoposide treatment was generally well tolerated, the most common side effect was neutropenia, in one case CTC grade 3. In conclusion, orally administered etoposide in metastatic Merkel cell carcinoma was highly effective and well tolerated.