Field surveys, well data and a detailed interpretation of a depth-converted seismic line, reveal that the Romanengo High, an isolated low relief that interrupts the morphological continuity of the Po Plain (N Italy) west of the Oglio River, coincides with a partially buried anticline, still active in recent times (Romanengo anticline). The Pliocene to Holocene evolution of the structure has been reconstructed by sequential restoration based on combined decompaction and unfolding methods, from the early Pliocene to Holocene. The analysis shows that from the beginning of the Pliocene onward, periods of tectonic activity have alternated with periods of quiescence. The more significant tectonic uplift rates are recorded during the late Pliocene (0.33 ± 0.06 mm/yr) and the beginning of Calabrian (0.284 ± 0.12 mm/yr), while at the end of Calabrian the structure was virtually inactive. During the early Pleistocene the reversal in the vergence of the structure indicates the onset of interaction with the Apennines deformational front in the area. From middle Pleistocene to Holocene, a marked increase in the tectonic uplift has been recorded, with an uplift rate of about 0.12 ± 0.05 mm/yr. A preliminary evaluation of the seismic hazards connected to blind thrusts affecting this active frontal sector of the Alpine chain, where it collides with the Apennines buried deformation fronts, is finally discussed.