After becoming dissatisfied with studies of canon law in Bologna, Pico began humanistic studies, first in Florence, where he made friends with Poliziano, then in Ferrara and in Padua. Aided by a famously prodigious memory, he studied Arabic literature and Hebrew cabalistic texts, as well as Latin and Greek classics, developing a special affection for Plato.

Pico tried to reconcile Greco-Roman, medieval Aristotelism and Judeo-Arabic thought with Cristian teaching. Such efforts were cut short by his early death. Much influenced by Plato, Pico accepted the ideal of amor socraticus between men. He expressed this kind of love with Girolamo Beniveni, ten years his junior, who ardently reciprocated his affections.

Their was, they declared, a fervent but chaste love kept under watch by rigorous morality and Christian misticism. However, during a sermon after Pico's death, Savonarola said that Pico committed a certain sin thath he did not wish to name. Five centuries later it is impossible to know the truth, but the probability that Pico made love with Beniveni in believable, as documents emerge showing the significance of homosexuality in the circle of Pico's friends.

He died suddenly, only two months after the equally sudden death of his friend Poliziano, who himself died shortly after a young male prostitute had accused him of infecting him, event though the converse is more likely true. Past historians hinted at death by poisoning, but more recent scholars suspect that Poliziano and Pico numbered among the first victims of the large-scale epidemic of syphilis, marked by acute symptoms and very rapid physicval deterioration, which broke out in Europe in 1493 and 1494.

It will never be known if Pico remained celibate or of his love for Beniveni was consummated. What is known is a delicate testimonial to this love: the tomb in which they decided to be buried together, and which can still be seen in the church of San Marco in Florence.