Non-invasive prenatal testing (NIPT) is a screening for foetal chromosomal abnormalities that identifies at-risk pregnancies and is used to propose a possible invasive genetic confirmation testing in case of its positive results. For Down syndrome (trisomy 21), its accuracy is close to 100%, while for other investigated conditions, it presents various limitations. In a neonate who presented with severe hypotonia and syndromic features, the NIPT was negative for all the screened anomalies. However, among the various investigations performed for the diagnosis, there was an altered methylation of the chromosomal region 15q11.2, indicative of Prader-Willi syndrome (PWS), previously excluded by NIPT. The paper therefore questions the significance of the results of this investigation in front of a clinical suspicion and reviews the use of NIPT in clinical practice.