Merkel cell carcinoma (MCC) is a rare neuroendocrine neoplasm of the skin. The tumor most frequently affects elderly patients, with a preference for the head and neck. Incidence rates increase with sun exposure and after immunosuppression and organ transplantation. A significant proportion of MCC have been reported to occur in intimate association with malignant epithelial neoplasms. The genetic mechanisms underlying the development and tumor progression of MCC are poorly understood, sharing pathogenetic mechanisms with other neoplasms of neural crest derivation. MCC has a propensity for spreading to regional lymph nodes, either at presentation or as a first site of relapse. Sentinel lymph node positivity is helpful in predicting the risk of recurrence or metastasis in patients with MCC. Complete surgical resection is the mainstay of treatment of the primary tumor. Tumor resections are recommended to include a 2-3-cm tumor-free margin around the primary lesion when possible, but this is often difficult to achieve in the head and neck, where Mohs micrographic surgery has proved to be effective. The role of adjuvant radiation therapy is controversial. 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. Overall survival of head and neck MCC at 5 years postoperatively ranks between 40% and 68%. MCC has a high incidence of locoregional recurrences, but even after a locoregional failure, a substantial proportion of patients achieve long-term disease-free survival. Finally, factors generally associated with survival are the stage of disease at presentation, distant recurrence usually being the most adverse predictor of survival.