p63 expression has been identified in several cohorts as a predictor of poorer prognosis in Merkel cell carcinoma. We used multivariate analysis in a large independent cohort to determine the clinical utility of this parameter. Immunohistochemistry was used to determine p63 expression on MCC tumors from 128 patients. Of these, 33% had detectable p63 expression. p63 positivity was associated with an increased risk of death from MCC (hazard ratio 2.05, p = 0.02) in a multivariate Cox regression model considering stage at presentation, age at diagnosis, and gender. Although p63 expression correlated with diminished survival in this largest cohort reported thus far, the effect was weaker than that observed in prior studies. Indeed, within a given stage, p63 status did not predict survival in a clinically or statistically significant manner. It thus remains unclear whether this test should be integrated into routine MCC patient management.