Abstract Merkel cell carcinoma (MCC) is a rare skin tumour of neuroendocrine origin with aggressive behaviour. The aims of this study were to investigate the association of p63 + MCC with clinicopathological features and to estimate survival through a systematic review and meta‐analysis. A comprehensive search of PubMed, Embase, Scopus and Virtual Health Library following the PRISMA guidelines was conducted on September 2017. DerSimonian and Lard random‐effects models were used to calculate survival‐weighted means and their corresponding 95% confidence intervals (CI) among studies. Five studies met our inclusion criteria after screening 77 citations and 36 full‐text articles. The included studies enrolled 413 patients with MCC. We observed that p63 + MCC was significantly associated with mortality with OR 2.92 (95% CI [1.66–5.13]). The summary hazard ratio of multivariate analysis was 1.99 (95% CI [1.32–3.01]). The only clinicopathological feature associated with p63 + MCC with statistical significance was the Merkel cell polyomavirus (MCPyV) status. The presence of MCPyV was associated as a protective factor for the expression of p63 (OR 0.25, 95% CI [0.08–0.73]). These results support that p63 + MCC evaluated by immunohistochemistry has a poor outcome. Therefore, we suggest p63 to be performed when staging MCC.