Merkel cell carcinoma is an unusual cutaneous malignancy with a propensity for spreading to regional lymph nodes, either at presentation or as a first site of relapse. Complete surgical resection is the mainstay of treatment of the primary tumor. Because the nodotrophic behavior of the tumor is recognized, lymphatic mapping with sentinel lymph node biopsy is becoming increasingly popular in the initial surgical staging of these patients. The role of elective lymphadenectomy in patients with clinically negative regional nodal basins is unknown. The role of adjuvant radiotherapy, either to the primary site or regional nodal basin, remains undefined. The role of adjuvant chemotherapy in diminishing the risk of subsequent systemic recurrence in patients with positive nodes remains undefined. Overall response rates to combination chemotherapy for surgically unresectable distant metastatic disease are generally high, although responses are transient.