Merkel cell carcinoma (MCC) is a rare neuroendocrine neoplasm, warranting surgical excision with sentinel lymph node biopsy. In later stages, adjuvant chemotherapy and radiation are required owing to its aggressive malignant behavior. We describe a 62-year-old woman who presented with multifocal recurrence of MCC and was not a candidate for immunotherapy or surgery. The patient underwent four treatments of intratumoral talimogene laherparepvec (TVEC) and demonstrated a complete response with no histologic evidence of remaining MCC on four scouting biopsies. Although TVEC therapy is currently approved for the treatment of advanced stage melanoma, it is still being investigated in MCC. This case supports the use of TVEC as monotherapy in select patients with locally advanced MCC who are not candidates for surgery or systemic immunotherapy.