We introduce a novel experimental methodology for the Reverse Phase Protein Microarray platform which reduces the typical measurement coefficient of variation as much as 70%. The methodology, referred to as Array Microenvironment Normalization, increases the statistical power of the platform. In experiment, it enabled the detection of a 1.1 fold shift in PSA concentration using approximately 6 technical replicates rather than the 37 replicates previously required. The improved reproducibility and statistical power should facilitate clinical implementation of the platform.