© Springer Science+Business Media, LLC 2016. Merkel cell carcinoma (MCC) is an aggressive carcinoma with neuroendocrine features that arises preferentially in chronically sun-damaged skin of elderly and immunosuppressed individuals. As the annual yearly incidence steadily increases, likely due to increased detection in an aging population, our understating of MCC continues to improve with recent discoveries. One such breakthrough is the characterization of the Merkel cell polyomavirus (MCPyV), which is present in up to 80 % of tumors, shedding light on MCC pathogenesis. MCC is characteristically composed of a monomorphous population of small round blue cells that express epithelial and neuroendocrine markers by immunohistochemistry. Immunohistochemical stains are invaluable in the diagnosis of this tumor and aid in excluding other histologic mimics. Regarding MCC prognosis, the strongest predictor for outcome is tumor staging, chiefly size of the tumor. Other recently added prognostic factors include the MCPyV status of the tumor, tumor thickness, and regional nodal involvement, including sentinel lymph node status. In this chapter, we will provide an update regarding the latest developments in terms of pathogenesis, immunohistochemical evaluation, and prognostic factors of MCC.