Known as "El Divino", most of his work was of religious subjects, including many representations of the Madonna and Child and the Passion.

Influenced, especially in his early work, by Raphael Sanzio and the Lombard school (fr) school of Leonardo, he was called by his contemporaries "The Divine Morales", because of his skill and the shocking realism of his paintings, and because of the spirituality transmitted by all his work.

His work has been divided by critics into two periods, an early stage under the influence of Florentine artists such as Michelangelo and a more intense, more anatomically correct later period similar to German and Flemish Renaissance painters.