Merkel cell carcinoma (MCC) is a highly aggressive neoplasm affecting primarily the elderly Caucasian population. Earlier detection of this neoplasm may achieve a better prognosis and an improved outcome. Here, the authors review the typical clinical features of MCC to serve as a reference tool for clinicians in determining when a biopsy may be warranted. An array of immunohistochemical markers may be utilized to differentiate MCC from other neuroendocrine tumors. The staging and concomitant treatment options of MCC are discussed. In addition, the authors review therapeutic advances for treatment of MCC utilizing an array of target proteins.