The Convent of San Marco owes its present appearance to the reconstruction of an earlier Medieval convent performed by the architect Michelozzo under commission to Cosimo the Elder, between 1436 and 1446. Three years after becoming state property in 1866, it became headquarters of a Museum housing many masterpieces, including the world-famous fresco cycle by Beato Angelico and most of his works on wood.

Though principally important from the historical-artistic viewpoint, the Museum also presents numerous elements of scientific interest: among the works by Angelico, it is only proper to cite the paintings conserved in the Pilgrims’ Hospice which portray the two physician saints, Cosma and Damiano, who are easily recognisable by their cassocks, red hats and the round box containing medicines. Exemplary among these is the painting on wood of the "Healing of the Deacon Justinian", in which the two saints are depicted in the act of transplanting the leg of a "moor" in replacement of the deacon’s diseased leg. Extremely interesting for the geographic disciplines is instead the San Marco Altarpiece, realised between 1438 and 1440: here, the Christ Child holds a terrestrial globe that modern scholars of ancient cartography have interpreted as a reference to the then known dry lands.

On the right wall of the passageway that connects the cloister of Sant’Antonino with the stairway that leads to the upper floor, the visitor can observe a cycle of four paintings by Jacopo Vignali, realised on the occasion of the plague of 1622-23 and intended for the convent "Spicery" (pharmacy). These paintings portray the theme of the disease and care of the body and spirit. On the opposite wall is the "Miracle of Saint Paul", a seventeenth-century work by Giovanni Bilivert, which presents an interesting curiosity: resting on the nose of one of the secondary figures is, in fact, a pair of eyeglasses, an object already widespread in the 16th century, and usually depicted in works of art as a symbol of knowledge and science.

The tie with science is even stronger, however, on the upper floor of the convent where, in addition to the cell of Cosimo with the fresco of the Adoration of the Magi in which there is a figure holding an armillary sphere, we also find the monumental Library by Michelozzo. The first public library of the Renaissance, it was born to conserve the books of humanist Niccolò Niccoli which were joined, by order of Cosimo the Elder, by the major texts of Medieval theological, legal and scientific knowledge. In the following centuries, the importance of the library, continually enriched with new volumes, was testified by mathematician and philosopher Gottfried Wilhelm von Leibniz who, in 1689, was able to consult a text of mathematical logic (the Liber calculationum by Richard Swineshead), which he had sought elsewhere in vain. The remains of a wind-rose, carved on a layer of plaster at the height of the library’s seventh western bay, indicate the former location of the collection of scientific books, which is also testified by a sixteenth-century catalogue of the convent’s works.

The San Marco complex is also tied to an episode that directly involved Galileo Galilei. In 1615, the Dominican Niccolò Lorini in fact denounced Galilei to the Inquisition, sending a copy of a letter in which the Pisan mathematician defended the validity of the Copernican theories. The Fathers of San Marco accused Galileo of having formulated «dubious or impudent» affirmations.