Ancillary testing in cytopathology has grown dramatically over the past decade, enhancing the clinical value of cytology specimens obtained via minimally invasive methods. However, a complex testing landscape brings with it new and emerging risks to patient safety. Recognition of complicated systems issues as well as shared responsibility in process ownership can help to minimize safety risks. Because pre‐analytic factors account for the majority of errors in pathology, attention to operational steps (test ordering, specimen collection, specimen transport, specimen accessioning, and specimen processing) is critical for successful quality improvement programs. With increasing technical costs and complexity of many ancillary molecular tests, a growing trend toward send‐out testing to centralized reference laboratories poses additional patient safety risks. Given these new realities in cytopathology ancillary testing, a collaborative, team‐based approach with all process stakeholders is needed to improve pre‐analytic processes, reduce error risk, and enhance patient safety.