In Denmark, the Faroe Islands, and Greenland, comprehensive screening of newborns for phenylketonuria and congenital hypothyroidism has been carried out for 20 years. The screening programme has detected 98 and 356 patients, respectively, corresponding to incidences of 1:12,000 and 1:3,400. The future savings on health care expenditures resulting from one year of neonatal screening are estimated to be 196 million DKK in present day value, which is 28 times higher than the cost of screening. The screening samples are stored in a biobank, which is used in diagnosis of congenital diseases and infant deaths and for development of future screening methods. It is desirable to expand the existing screening programme to include a range of rare inherited metabolic diseases, which collectively are frequent. This is realistic with the advent of tandem mass spectrometry, which allows cost-effective simultaneous screening for a group of inborn errors of metabolism.