Vasco de la Zarza employed Italianate forms in the alabaster tomb of Bishop Alonso de Madrigal (el Tostado). Lucas Giraldo (fl 1529-1544), carved the trascoro (screen; 1531-1536) with the Infancy of Christ and rich Plateresque decoration.

Building began with the five ambulatory chapels enclosed by the semicircular wall that formed part of the city ramparts. The design draws on Burgundian sources, but it also shows a wider awareness of Early Gothic experiments in northern France. The double ambulatory with slender columns is derived from Saint-Denis Abbey and other Ile-de-France buildings. In the 13th century a sacristy with a complex rib vault, a chapter house with eight-part vault and squinches and a cloister were added, but construction slowed in the nave. Juan Guas was commissioned for a chapel in the cloister in 1471, and Martín de Solórzano designed the library (Capilla del Cardenal) in 1495. Other Renaissance work was done up to 1603.