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Background: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine neoplasia, with high risk of recurrence and metastasis and poor survival. Immune checkpoint inhibitors, like the anti-programmed death-ligand 1 agent avelumab, were recently approved for the treatment of advanced MCC. We, herein, report the first case of advanced MCC with oligoprogression managed with avelumab and local radical treatment., Case Summary: A 61-year-old man was presented to the hospital with sporadic fever and an exudative malodorous mass (10 cm of diameter), located on the right gluteal region. The final diagnosis was MCC, cT4N3M1c (AJCC, TNM staging 8 th edition, 2017), with invasion of adjacent muscle, in-transit metastasis, and bone lesions. Patient started chemotherapy (cisplatin and etoposide), and after six cycles, the main tumor increased, evidencing disease progression. Two months later, the patient started second line treatment with avelumab (under an early access program). After two cycles of treatment, the lesion started to decrease, achieving a major response. Local progression was documented after 16 cycles. However, as the tumor became resectable, salvage surgery was performed, while keeping the systemic treatment with avelumab. Since the patient developed bilateral pneumonia, immunotherapy was suspended. More than 2.5 years after surgery (last 19 mo without systemic therapy), the patient maintains complete local response and stable bone lesions., Conclusion: This report highlights the efficacy and long-term response of avelumab on the management of a chemotherapy resistant advanced MCC, with evidence of oligoprogression, in combination with local radical treatment., Competing Interests: Conflict-of-interest statement: Dr. Marinho reports grants from Merck KGaA, during the conduct of the study; personal fees from Merck KGaA, non-financial support from Servier, non-financial support from Astellas, non-financial support from Roche, non-financial support from Lilly, non-financial support from Merck, outside the submitted work. "The patient was treated in the expanded access program and avelumab was provided by Merck KGaA, as part of an Alliance between Merck KGaA and Pfizer". The development of this publication was financially supported by Merck KGaA, Darmstadt, Germany through an independent medical writing grant, as part of an Alliance between Merck KGaA and Pfizer. The views and opinions described in this publication do not necessarily reflect those of the grantor., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)