Going beyond the violent imagery conventional to Italian representations of the subject, Domenico Ghirlandaio’s Massacre of the Innocents (1485–1490) presents an unsettling mixture of dazzling beauty and graphic violence. The fresco, located in the high chapel of the Florentine church of Santa Maria Novella, juxtaposes sumptuous fabrics and gleaming metal surfaces with bloodied and broken infant bodies. While representations of the Massacre often featured piles of mangled corpses, the prominent inclusion in the fresco of pieces of the Holy Innocents – severed heads and arms – was a highly atypical divergence from the established iconography of the scene. This article considers how the depiction of body parts in the Ghirlandaio fresco – and in a related painting of the same subject by Matteo di Giovanni – shaped the viewing experience. I argue that in their original devotional context, these paintings would have fostered a ‘reliquary mode of seeing’ by combining formal features characteristic of reliquaries with the representation of relic-like body fragments. Furthermore, the relationship with reliquary devotion was made exceptionally palpable and immediate by the presence of relics of the Holy Innocents in the churches were both paintings were located. The body parts in the paintings thus would have served as metonyms for the relics themselves: the depicted heads and limbs framed with painted signs of material splendor, the actual relics encased in precious materials.