This work presents the first results from the Aguilón P5 (Zaragoza) cave site on the northern slope of the Iberian System (NE Iberia). The fieldwork carried out since 2010 on several archaeological layers containing remnants of human occupations has revealed lithic remains, processed faunal bones and charred plant remains from combustion events. Due to the lithic tool assemblage and radiocarbon dating (>50.0–41.9 kyr BP), the attribution of this human occupation to the Mousterian techno-complex is clear, contemporary with other important Late Mousterian sites in the Ebro Basin (NE Iberia) and Mediterranean region. Preliminary results concerning stratigraphic, chronometric, techno-tipological and palaeoenvironmental data from the last human occupations of the cave (archaeological layers “cnc”, “mcp” and “e”) are provided in this paper.To contextualize the Neanderthal occupation of the Aguilón P5 cave, a timeline of Middle Paleolithic in the Iberian System is proposed. A total of 45 dates from 19 stratigraphic units (including speleothems) are available from 10 sites. Chronometric dating series allow us to establish the temporary framework of Mousterian industries in the Iberian System coinciding with the abrupt climate changes related to Heinrich Events which characterize MIS 3. In summary, this paper provides new chronometric and archaeological information about Neanderthal settlement and subsistence in an under-investigated region.