Purpose: Merkel cell carcinoma of the skin is a rare, but aggressive malignancy that predominantly affects older adults with fair skin. Isolated limb infusion using melphalan and actinomycin D was first developed as a minimally invasive treatment option to treat unresectable metastatic melanoma confined to the limb. We report on a 62-year-old male with in-transit metastasestreated with an isolated limb infusion to highlight the ongoing role this treatment has when all other therapies have been exhausted. Methodology: The patient was initially treated with a wide local excision, followed by adjuvant radiotherapy. He subsequently developed in-transit metastases, which were treated with avelumab. Progressive nodal disease was later noted involving the inguinal and iliac lymph nodes and a groin dissection was performed. At presentation, the patient had widespread in-transit metastases in the right leg. The patient was treated with an isolated limb infusion andprogressed well in the immediate post-operative period. Results: On day three post isolated limb infusion, the patient was commenced on intravenous dexamethasone due to increased pain on dorsiflexion. Creatinine kinase reached a peak of 1742 U/L the following day. He was able to mobilise from day 6, and was discharged on day 10. There was an immediate clinical response seen in the lesions, with necrosis developing in the larger lesions. Conclusion: The authors present this case to highlight that there is an ongoing role for isolated limb infusions in those patients with a significant burden of in-transit metastases in Merkel cell carcinoma that have exhausted treatment modalities in this era of immunotherapy.