Middle Pleistocene continental sediments in central Italy ("Qc Unit") record the oldest fluvial accumulation along the uplifting margin of the Peri-Adriatic basin. The architecture of the sediment body can be divided into two unconformity-bounded, fining-upward cycles interpreted as genetically related depositional sequences. These sequences highlight the systematic adjustment of the fluvial system to changes in the ratio between accommodation space and sediment supply (A/S ratio) and from base to top, comprise the following surfaces and stratal components: (i) a regionally correlative sequence boundary resulting from an A/S ratio ≤ 0; (ii) a low-accommodation systems tract characterized by conglomerate-rich, amalgamated channel fills and recording an A/S ratio < 1; (iii) an expansion surface marking the turnaround point from low-accommodation systems tract to high-accommodation systems tract deposits; (iv) a high-accommodation systems tract dominated by floodplain fines encasing lens-like, fluvial channel deposits and denoting an A/S ratio > 1; and (v) a mature red argillic paleosol. To constrain the climatic signal for paleosols formation, the two sequence-capping mature paleosols have been investigated. The results of these studies suggest that they were developed under humid and warm climatic conditions associated with interglacial phases, which have been correlatively attributed to Marine Oxygen Isotope Stages 11 and 9.