[2] That was a new illness that spread to Europe from the Americas at the end of the 15th century and that was taken to Italy from the troops of the French king Charles VIII of France.

In those same years, Girolamo Fracastoro, a pioneer of the modern pathology, proposed a cure for syphilis, the expensive Lignum vitae, that was soon offered to the patients of San Giacomo for free.

The hospital was rebuilt in the second half of 16th century mainly by the activity of cardinal Antonio Maria Salviati, together with the Church San Giacomo in Augusta, ended in the year 1600.

The condition of the donation of Salviati was confirmed in 1610 by the papal bull in form of motu proprio by the pope Paulus V.[citation needed] During the 16th century Camillus de Lellis was active in the Hospital.

[7] In 1780 Pius VI built the round-shaped room with Anatomical theatre in the Sala Lancisiana, named after the surgeon Giovanni Maria Lancisi.

[10] In the mid-19th century the Pope Gregory XVI made some major rebuilding work on the hospital structure,[6] with the help of both public and personal economic funding.

[18] On April 7, 2021 the Consiglio di Stato (Council of State) sentenced that the closing of San Giacomo was "illegitimate" according to the italian law, as a result of the long legal dispute with Oliva Salviati.