Placenta accreta spectrum (PAS) is a group of pregnancy pathologies characterized by loss/absence of decidua and trophoblast over-invasion penetrating into the myometrium beyond the normal depth. It is associated with expansion of deeper branches of the uterine arteries and placental adherence to the uterus. Undetected PAS leads frequently to massive and potentially fatal hemorrhage at delivery. For the more severe forms of PAS (increta, percreta), the most frequent solution is caesarean delivery-hysterectomy. The etiology of PAS is, however, unclear at best. While there is increasing research interest, the clinical intricacies of this pathology pose significant challenges for the researcher. In this communication we present the elements which we believe should be considered when undertaking (or interpreting) research into PAS, particularly when biological samples and molecular techniques are involved.