Mislabeled umbilical cord blood specimens were identified as an important and difficult problem to solve. Quality improvement principles were employed after education-based interventions failed to achieve measurable improvement. A small interdisciplinary working group of key stakeholders investigated, designed, and evaluated interventions for a solution. This article describes a system-based change where substantial qualitative and quantitative improvements were measured. The success of the change is attributed to the involvement and commitment by key stakeholders and use of systems reengineering principles.