During his sojourns in Rome, 1585–95 and 1597–1601, Cardinal Borromeo envisioned developing a library in Milan as one open to scholars and that would serve as a bulwark of Catholic scholarship in the service of the Counter-Reformation against the treatises issuing from Protestant presses.

There was only one large block purchase; attempts to buy the library of Cardinal Ascanio Colonna in Rome and those of Giacomo Barocci and Pietro Bembo in Venice were unsuccessful, though Lucrezia Borgia's love-letters presumably came from the last.

The most valuable codex obtained in this way was perhaps the sixth-century papyrus Josephus from Sant'Ambrogio in Milan, and the greatest coup, the acquisition of part of Bobbio's ancient library in exchange for 'more useful' modern books.

Bobbio had been founded in the early seventh century by a party of Irish monks under St Columban, and still owned the only substantial group of Italian pre-Caroline manuscripts outside Verona Cathedral.

Cardinal Federigo chose a suitable envoy, Gian Giacomo Valeri, of an old Milanese family, Canon of Santa Maria della Scala and an antiquarian collector on his own account.

He owned works in Glagolitic (the medieval alphabet of Croatia) and a Japanese Contemptus mundi printed in Amakusa in 1596, and begged Cardinal Ottavio Bandini’s secretary to find him hieroglyphic books.

Two hundred volumes of transcripts of state papers were impounded by the Republic of Venice and more books were lost when Barbary pirates attacked the galleys carrying the consignment down the Adriatic to the collector's Neapolitan heirs.

[1] Rooms to hold collections of pictures and casts of antique statues, to which was later added accommodation for schools of painting and sculpture, occupied the remainder of a long narrow building adjoining the churches of San Sepolcro and Santa Maria della Rosa in the centre of Milan.

Artwork at the Pinacoteca Ambrosiana includes Leonardo da Vinci's Portrait of a Musician, Caravaggio's Basket of Fruit, Bramantino's Adoration of the Christ Child and Raphael's cartoon of "The School of Athens".

In 1637, six years after the cardinal's death, the library acquired twelve manuscripts of Leonardo da Vinci, including the Codex Atlanticus, from the Marquis Galeazzo Arconati, who had refused a tempting offer from Thomas Howard, Earl of Arundel.

Among the 30,000 manuscripts, which range from Greek and Latin to Hebrew, Syriac, Arabic,[3] Ethiopian, Turkish and Persian, is the Muratorian fragment, of ca 170 A.D., the earliest example of a Biblical canon and an original copy of De divina proportione by Luca Pacioli.

Gian Vincenzo Pinelli's library, purchased by Cardinal Borromeo in 1608, comprises five hundred and fifty manuscripts, including a fourth- or fifth-century illustrated Homer known as 'the Ambrosian Iliad', a tenth- or eleventh-century Horace, a copy of Dante's Divine Comedy written in Padua about 1355, Boccaccio's La Fiammetta annotated by Pietro Bembo, and many antiquarian, humanistic and topical miscellanies.

Among the treasures of the library are also a Greek Pentateuch of the fifth century; several palimpsest texts, including an early Plautus, fragments of Ulfilas's Gothic Bible, and a copy of Virgil, with marginal notes by Petrarch.

Manuscripts and incunables had been removed and escaped intact, and the damage to the fabric was made good after the war (the paintings are now particularly well displayed), but several volumes perished, including the archives of opera libretti of La Scala.