Newborn screening continues to progress as a public health program aimed at the identification of pre-symptomatic newborns with potentially serious or fatal disorders for which early intervention can prevent mortality and morbidity. Severe combined immune deficiency (SCID) was recognized as a disorder that meets newborn screening criteria and was unanimously recommended to be added to the core panel in 2010 by the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC). SCID is a group of rare and often fatal inherited disorders characterized by the absence of both humoral and cellular immunity. SCID is comprised of at least 15 genetic conditions, leading to variable disease presentation, but common characteristics include failure to thrive and opportunistic infections associated with marked lymphocytopenia in the first months of life. Untreated, children with SCID have near-uniform mortality by 1 year of age (5). The average age of diagnosis for infants who present clinically is just over 6 months (2) and it is estimated that up to 50% of infants die because they are diagnosed too late for life-saving therapies (4). The Minnesota Newborn Screening Program (MDH) has already begun collaboration with the Cellular and Molecular Immunology Laboratory (part of the Jeffrey Modell Foundation for Primary Immuno-deficiencies Diagnostic and Research Center) at the Mayo Clinic to create a comprehensive SCID intervention plan, which will utilize the MDH Newborn Screening Program, diagnostic laboratory evaluation via flow cytometry at Mayo Clinic, clinical immunologists, and secure web-based technology for real-time communication and follow-up. MDH is also an active participant in the Region IV Genetics Collaborative, which recently launched a SCID screening application. Participation in this application will provide MDH another opportunity for continuous quality improvement as we compare our testing metrics with other laboratories and nationwide cumulative data. Our program builds on a long history of quality education, testing, and follow-up for newborn screening, which will be drawn upon during the implementation of newborn screening for SCID. Our goal is to develop an effective and efficient approach to SCID screening that will serve as a model for other states and new disorders to come.