The worldwide spread of COVID-19 has stressed clinical laboratories in numerous dimensions including supply chain management, preanalytical throughput, analytical throughput, and extreme variances in testing demand. Innovative tests, such as the TaqPath COVID-19 Combo Kit, build on the strong technical foundation and substantial manufacturing capacity of Thermo Fisher Scientific while also leveraging the workforce of molecular biologists trained and experienced in real-time PCR techniques in order to address an unprecedented scale-up in test capacity required. Whether in a start-up laboratory or a well-established laboratory, successful ongoing testing with the TaqPath COVID-19 Combo Kit that is responsive to the needs of patients and physicians requires acute attention to detail in traditional areas of laboratory operations including quality control, workflow, labor allocation, standardized processes, and technician training, but the open format of the assay and associated analyses add additional challenges. This presentation will illustrate how the TaqPath COVID-19 Combo Kit is operationalized at a large regional reference laboratory with particular emphasis on the challenges unique to the assay.