Protein detection strategies that will have a positive impact on cancer diagnosis must be highly sensitive, very specific, and utilize time-and cost-effective methods. We report on the development of a method that fulfills these criteria by using a nanowire-based electrode platform that enables use of an electrochemical reporter system for protein detection. The prostate-specific antigen is detected with peptide-modified nanowires. An electrocatalytic reporter system is used to transduce the activity of the enzymes into a measurable electrochemical signal that accurately reports on physiologically relevant picomolar quantities of the analytes.