Serum pregnancy-associated plasma protein-A (PAPP-A) is measured in Down\'s syndrome screening, routinely offered to women in pregnancy. We present the case of an undetectable pregnancy-associated plasma protein-A concentration on the PerkinElmer AutoDELFIA system where immunoassay interference was suspected. Investigations performed, including dilution and recovery studies and antibody-blocking tube incubations, all yielded serum pregnancy-associated plasma protein-A concentrations of <25 mU/L. Pregnancy-associated plasma protein-A was also undetectable on two alternative pregnancy-associated plasma protein-A assays. An experimental manual Delfia procedure suggested the site of interference was between the secondary antibody and the pregnancy-associated plasma protein-A molecule. This case of negative interference in the PerkinElmer pregnancy-associated plasma protein-A assay produced a falsely high Down\'s syndrome risk that might have led to an unnecessary invasive procedure with the potential for fetal loss. This highlights the need for Down\'s syndrome screening laboratories to be vigilant to immunoassay interference due to the significant impact of the results on patient decision outcome.