Lorenzo de' Medici, the autocrat of Florence and the chief patron of learning in Italy at the time, took Poliziano into his household, made him the tutor of his children,[6] among which were Piero the Unfortunate and Giovanni, the future Pope Leo X.

Among Poliziano's pupils could be numbered the chief students of Europe, the men who were destined to carry to their homes the spolia opima of Italian culture.

It was the method of professors at that period to read the Greek and Latin authors with their class, dictating philological and critical notes, emending corrupt passages in the received texts, offering elucidations of the matter, and teaching laws, manners, religious and philosophical opinions of the ancients.

Poliziano covered nearly the whole ground of classical literature during his tenure, and published the notes of his courses upon Ovid, Suetonius, Statius, Pliny the Younger, and Quintilian.

Poliziano wrote a letter to John II of Portugal paying him a profound homage: and considering his achievements to be of merit above Alexander the Great or Julius Caesar.

[9] Evidence includes denunciations of sodomy made to the Florentine authorities, poems and letters of contemporaries, and allusions within his work (most notably the Orfeo).

[10] Prior to his exhumation in 2007, the circumstances of his death were also sometimes considered to be evidence of homosexuality: some evidence suggested that he was killed by a fever (possibly resulting from syphilis) which was exacerbated by standing under the windowsill of a boy he was infatuated with despite being ill.[11] Others thought that his death was precipitated by the loss of his friend and patron Lorenzo de' Medici in April 1492, Poliziano himself dying on 24 September 1494, just before the foreign invasion gathering in France swept over Italy.

[12] Forensic tests showed that both Poliziano and Pico likely died of arsenic poisoning, possibly the order of Lorenzo's successor, Piero de' Medici.

[13] Poliziano was well known as a scholar, a professor, a critic, and a Latin poet in an age when the classics were still studied with assimilative curiosity, and not with the scientific industry of a later period.