The plan, originally a Greek cross with a large dome where the cross meets, is now a Latin cross, divided into five naves with apse and transept with aisles. The striking effect of the architectural spaces is reminiscent of the great mosques thanks to the use of raised round arches alternating with bands in black and white marble and the unusual Moorish-style elliptical cupola. The presence of the two raised matronea in the naves clearly have Byzantine influences. The pointed arches allude to Muslim influences in Southern Italy. The blind arches with lozenges are similar to Armenian churches. The interior is covered in white and black marble with monolithic columns in grey marble and Corinthian capitals.
The 17th-century coffered ceiling is by Florentines Domenico and Bartolomeo Atticciati. At the point where the transepts and central part of the building meet the dome rises up, frescoed with the Virgin Mary amid Glory and Pisan Saints Orazio and Girolamo Riminaldi (1627-31). The Corinthian-style granite columns between the nave and the apse come from the Palermo Mosque, the spoils of the battle in the Cala dai Pisani in 1063. The great apsidal mosaic of Christ on the throne between the Virgin Mary and Saint Giovanni is famous thanks to the face of Saint Giovanni designed by Cimabue in 1302, and which miraculously survived the 1595 fire. Also a survivor of the fire is the medieval Cosmatesque floor (12th century) beneath the triumphal arch, a rare gem outside Lazio. It was made in marble inlay with “opus alexandrinum” geometric motifs.
The pulpit by Giovanni Pisano (1302-10) is, due to its complex architectural and sculptural decoration, one of the largest narrations in 14th-century imagery. Its curved panels tell stories from Christ’s life. It is widely regarded as the artist’s masterpiece as well as in the whole of Italian Gothic sculpture. The 27 paintings that cover the tribune behind the main altar – depicting episodes from the Old Testament and stories of Christ – were created from the 16th and 17th centuries by some of the foremost Tuscan artists, including Andrea del Sarto, il Sodoma and Domenico Beccafumi.