The risk of second cancers in Merkel cell carcinoma (MCC) remains uncertain since risk estimates vary worldwide. The global MCC population is growing and there is a demand for better knowledge of prognosis of this disease. The Cochrane Database of Systematic Reviews, MEDLINE, and EMBASE search engines were searched for the relevant literature between January 1999 and September 2014 by use of explicit search criteria. The main outcome was second malignancies associated with MCC patients measured by standardized incidence ratios (SIRs) or other estimates of risks. Five papers fulfilled the inclusion criteria and reported SIRs of second cancer in MCC which varied from 1.07 to 2.80. Performing meta-analysis using random effects model revealed that there was an increased risk for second malignancies due to MCC (SIR, 1.52; 95% CI, 1.10–2.11). There was a significant increase in risk for malignant melanoma (SIR, 3.09; 95% CI, 2.02–4.73) as compared to all common second malignancies among the studies. Updated knowledge about risk of second malignancies in MCC will help in better assessment of the disease prognosis and will help in optimizing the medical and surgical treatment, radiotherapy, follow-up, and surveillance procedures. 1. Introduction Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine tumor, was first reported in 1972 as a variant of “trabecular carcinoma of the skin” [1]. Studies based on Survival Epidemiology and End Result Program (SEER) have shown that estimated age-adjusted incidence rate for MCC was as low as 0.18 to 0.41 per 100,000 population by the year of 2006 [2]. Subsequent studies have estimated a fourfold increase in incidence over the last two decades [3, 4]. Prognosis of this cancer is very poor because this cancer grows rapidly and has high risk for early metastasis [5, 6]. MCC is essentially the tumor of Merkel cells, which are cells derived from the proliferative keratinocyte layer of skin [7–9]. Exposure to ultraviolet (UV) radiation, reactive oxygen species, and arsenic as well as immunosuppression are some of the known risk factors for this malignancy [10–12]. Some studies also suspect a rare polyomavirus as the probable causative agent [13]. This virus was demonstrated in 80% of all MCC tumors and was successively named Merkel cell polyomavirus (MCPyV) [14]. Currently, biopsy is the main procedure for diagnosis of MCC. Immunohistochemical staining and electron microscopy have greatly advanced the diagnostic accuracy [15]. MCC stains like neuron-specific enolase, synaptophysin, chromogranin, cytokeratin 20, and
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