With bewildering attainments due to his brilliant and tenacious memory, he returned to Rome in 1486 and undertook to maintain 900 theses on all possible subjects (Conclusiones philosophicae, cabalasticae et theologicae, Rome, 1486, in fol.). He offered to pay the expenses of those who came from a distance to engage with him in public discussion. Pope Innocent VIII was made to believe that at least thirteen of these theses were heretical, though in reality they merely revealed the shallowness of the learning of that epoch. Even such a mind as Pico's showed too much credulity in nonsensical beliefs, and too great a liking for childish and unsolvable problems. The proposed disputation was prohibited and the book containing the theses was interdicted, notwithstanding the author's defence in Apologia J. Pici Mirandolani, Concordiae comitis (1489). One of his detractors had maintained that Kabbala was the name of an impious writer against Jesus Christ. Despite all efforts Pico was condemned, and he decided to travel, visiting France first, but he afterwards returned to Florence. He destroyed his poetical works, gave up profane science, and determined to devote his old age to a defence of Christianity against Jews, Mohammedans, and astrologers. A portion of this work was published after his death (Disputationes adversus astrologiam divinatricem, Bologna, 1495). Because of this book and his controversy against astrology, Pico marks an era and a decisive progressive movement in ideas. He died two months after his intimate friend Politian, on the day Charles VIII of France entered Florence. He was interred at San Marco, and Savonarola delivered the funeral oration.
Besides the writings already mentioned, see his complete works (Bologna, 1496; Venice, 1498; Strasburg, 1504; Basle, 1557; 1573, 1601). He wrote in Italian an imitation of Plato's Banquet. His letters (Aureae ad familiares epistolae, Paris, 1499) are important for the history of contemporary thought. The many editions of his entire works in the sixteenth century sufficiently prove his influence.