Death has always been a topic of extreme fascination for man, a source of angst that has dominated artworks and the human imagination since time immemorial. Every era abounds with symbols for the transient nature of our earthly existence, but one stands out above all: the skull, that often “meditative” simulacrum that warns us of the futility of all worldly things and forces us to ponder the meaning of life. The definitive emblem of Vanitas, the skull crops up in Medieval imagery, topping off putrefying bodies that lie in wait for careless wayfarers. Stripped of its flesh, down to the bare bone, in the Renaissance the skeleton began the rise towards its seventeenth century pinnacle. Yet subsequently this image encountered varying fortunes. In the eighteenth century it lost most of its macabre connotations with the resurgence of subgenres connected to the memento mori, yet without dissipating its power. And while in the nineteenth century it made a half-hearted return, it was in the twentieth century that it regained much of its previous popularity. The turn of the millennium saw it on the crest of the wave, with skulls and skeletons once more dominating the visual arts. However this exponential increase in popularity, in quantity rather than quality, did not automatically correspond to a renewed power: art appears to be inured to the point of insensitivity to image of the skull. Inert, incapable of inspiring fear or imposing a moral agenda, the death’s head appears to have lost all its previous emphasis. This is the diagnosis reached by the author of Frenologia della vanitas after a long and complex exploration that seeks out unusual combinations and forges connections between past and present, styles and periods. The decision not to adopt a chronological structure or other forms of classification enables the arguments to develop rhizomatically, played out against the author’s underlying apprehension for the future of the skull.