Recently, the total prostate-specific antigen (PSA) assay used in a laboratory had a positive bias of 0.03 μg/L, which went undetected. Consequently, a number of post-prostatectomy patients with previously undetectable PSA concentrations (defined as <0.03 μg/L in that laboratory) were being reported as having detectable PSA, which suggested poorer prognosis according to clinical guidelines. Through numerical simulations, we explored (1) how a small bias may evade the detection of routine quality control (QC) procedures with specific reference to the concentration of the QC material, (2) whether the use of 'average of normals' approach may detect such a small bias, and (3) describe the use of moving sum of number of patient results with detectable PSA as an adjunct QC procedure. The lowest QC level (0.86 μg/L) available from a commercial kit had poor probability (<10%) of a bias of 0.03 μg/L regardless of QC rule (i.e. 1:2S, 2:2S, 1:3S, 4:1S) used. The average number of patient results affected before error detection (ANPed) was high when using the average of normals approach due to the relatively wide control limits. By contrast, the ANPed was significantly lower for the moving sum of number of patient results with a detectable PSA approach. Laboratory practitioners should ensure their QC strategy can detect small but critical bias, and may require supplementation of ultra-low QC levels that are not covered by commercial kits with in-house preparations. The use of moving sum of number of patient results with a detectable result is a helpful adjunct QC tool.