Patronised by the confraternity of the church, the Palatine Chapel is a wonderful example of Gothic and Renaissance art. Dating back to the first half of the 16th century, it has a square plan concluded by a hemispherical dome. The entrance portal to the chapel consists of columns and half-columns decorated with grotesque motifs. On the sides are grotesque figures with flaming lion heads and suns that turn into moons. Inside the chapel, in the niche above the altar, is a statue of the Madonna of Bethlehem, a stone sculpture dating back to the 16th century. To the left is an aedicule containing a reliquary urn dating back to the 17th century surmounted by the de Leva family coat of arms. On the right wall of the chapel is the asphaltic stone tomb slab of Don Francesco Lorefice, who died at the age of twenty in 1779. The chapel, consisting of a square base, changes its shape to an octagon, at the corners of which are Byzantine-Norman style pendentives. In the dome are roundels depicting Roman emperors.

The floor is made of Caltagirone majolica. Around 1750, the entire church was being paved with these tiles and it must have been special to have such a large and decorated space. It was not finished because of the fragility of the majolica tiles, which meant they had to be continually replaced. Eventually it was decided to pave the church with this white Carrara marble floor (1888).

Above the door of the Sacristy is the canvas of the Consolation of Mary, which is based on the painting of the same name in the Church of S. Maria del Carmine (see the dedicated sheet).

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