International Neonatal Screening Day is observed worldwide every June 28 to emphasize the importance of timely diagnosis for serious congenital disorders in newborns that require immediate treatment. The day was initiated in 2021 by the International Society for Neonatal Screening, the European Society for Immunodeficiencies, and the International Patient Organization for Primary Immunodeficiencies, coinciding with the birthday of American microbiologist Robert Guthrie, who developed a method for screening phenylketonuria (PKU) at birth. Newborn screening programs vary by country, with Italy screening for 49 conditions, while the United States allows each state to determine its own panel of disorders. The primary aim of the observance is to highlight the critical role of neonatal screening in preventing potentially debilitating and life-threatening conditions, promoting the exchange of expertise and further research in this field.