The church houses the relics of St Antoninus of Florence and the tomb of Pico Della Mirandola, a Renaissance philosopher known as the "Father of Humanism."

In 1418 the Sylvestrines, accused of laxity in their observance of the Rule, were pressured to leave, but it took a direct intervention of Pope Eugene IV and the Council of Basel before finally in 1437 the San Marco buildings were vacated, the displaced Sylvestrines moved to the smaller monastery of San Giorgio alla Costa.

A decisive element in securing the move was the intervention of Cosimo de' Medici the Elder, who since 1420 had already shown his support for the reformed Franciscan convent of Bosco ai Frati.

On their arrival, the new residents found the San Marco buildings in poor condition, so much so that for two years or so they were obliged to live in damp cells or wooden huts.

In 1437 Cosimo commissioned Michelozzo, the Medici family's favourite architect, to rebuild the San Marco convent on Renaissance lines.

By 1438 the work was well underway and the final dedication took place on Epiphany night 1443 in the presence of Pope Eugene IV and the Archbishop of Capua, cardinal Niccolò d'Acciapaccio.

The work was planned according to arrangements that took account of simplicity and practicality, but were of great elegance: a sober, though comfortable, Renaissance edifice.

On the upper floor were the friars' cells, small walled enclosures overarched by a single trussed roof.

He was to fall foul of the court of Pope Alexander VI Borgia and ended his life burnt at the stake in front of the Palazzo della Signoria in 1498.

Until recently San Marco still housed a community of Dominican friars, who occupied the Western part of the complex adjacent to the larger cloister.