The management of upper urinary tract urothelial carcinoma (UUT-UC) is controversial. Radical nephroureterectomy is a major undertaking and has obvious shortcomings in the presence of renal impairment and solitary kidneys, whereas endoscopic management can be associated with a risk of disease progression. There is a pressing need for reliable predictive biomarkers to refine patient selection for renal conservation. p53 is the most frequently investigated molecular marker in UUT-UC. Of the 24 papers published on the subject, expression of p53 is a significant univariate prognostic marker in 12 publications, representing seven unique cohorts. However, multivariate analysis demonstrates that p53 expression is of independent prognostic significance in only five studies, all of which contain potential statistical bias. The currently available data do not, therefore, support a role for p53 in this regard, and suggest a need for prospective large-scale collaborative studies using standardized methods of p53 detection and statistical analysis.