Coupling anatomic pathology work cells with a macrosystem construct creates a decision-making perspective that can improve service quality, reduce risk, and enhance patient safety. The authors examine recent changes that have had an impact on anatomic pathology macrosystems, the evolving macrosystem tactics to ensure maintenance of patient safety, and macrosystem change theory. They explore the usefulness of high reliability organization theory and normal accident theory. They conclude with an analysis of the potential for enhanced patient safety through macrosystem consolidation, standardization, and communication in a best care algorithm based on outcome analysis.