Piero di Cosimo was terrified of thunderstorms, could not bear the sound of coughing, crying babies, chanting friars or church bells, and reportedly lived on a diet of hard-boiled eggs, which he cooked fifty at a time while boiling glue for his paintings. Giorgio Vasari, who compiled these details, described him as living "more like a beast than a man". He let his garden run wild on principle, preferring to see plants and animals free of cultivation.

He was born in Florence around 1462, took the name di Cosimo from his master Cosimo Rosselli, and by 1480 was working as an unpaid apprentice in Rosselli's workshop. He operated outside the official artistic circles of Florentine Renaissance painting, borrowing freely from Leonardo, Signorelli and Netherlandish artists without belonging to any school.

His mythological paintings, many based on Vitruvius's account of human evolution, are filled with hybrid creatures, fantastic landscapes and strange revels. He also painted portraits, including the posthumous bust of Simonetta Vespucci (c. 1480), and excelled at designing pageants and triumphal processions for Florentine festivals. He could discern equestrian battles and urban scenes in the stains on a wall, a habit Leonardo also described. He died in Florence in 1521.