S U M M A R Y Geophysical data from the MEDOC experiment across the Northern Tyrrhenian backarc basin has mapped a failed rift during backarc extension of cratonic Variscan lithosphere. In contrast, data across the Central Tyrrhenian have revealed the presence of magmatic accretion followed by mantle exhumation after continental breakup. Here we analyse the MEDOC transect E–F, which extends from Sardinia to the Campania margin at 40.5 • N, to define the distribution of geological domains in the transition from the complex Central Tyrrhenian to the extended continental crust of the Northern Tyrrhenian. The crust and uppermost mantle structure along this ∼400-km-long transect have been investigated based on wide-angle seismic data, gravity modelling and multichannel seismic reflection imaging. The P-wave tomographic model together with a P-wave-velocity-derived density model and the multichannel seismic images reveal seven different domains along this transect, in contrast to the simpler structure to the south and north. The stretched continental crust under Sardinia margin abuts the magmatic crust of Cornaglia Terrace, where accretion likely occurred during backarc extension. Eastwards , around Secchi seamount, a second segment of thinned continental crust (7–8 km) is observed. Two short segments of magmatically modified continental crust are separated by the ∼5-km-wide segment of the Vavilov basin possibly made of exhumed mantle rocks. The eastern segment of the 40.5 • N transect E–F is characterized by continental crust extending from mainland Italy towards the Campania margin. Ground truthing and prior geophysical information obtained north and south of transect E–F was integrated in this study to map the spatial distribution of basement domains in the Central Tyrrhenian basin. The northward transition of crustal domains depicts a complex 3-D structure represented by abrupt spatial changes of magmatic and non-magmatic crustal domains. These observations imply rapid variations of magmatic activity difficult to reconcile with current models of extension of continental lithosphere essentially 2-D over long distances.