Colegio de Santa Cruz de Tlatelolco, Baroque educational institution in Tlatelolco, Mexico.

The Colegio de Santa Cruz de Tlatelolco is a stone building whose facade is built of rough grey and brown masonry blocks, with two square towers at the edges, each pierced by arched openings and topped by a small cornice. The lower central section ends in a curved gable with a small circular emblem; below it, a light-grey carved stone frame surrounds a rectangular window, and the round-arched entrance has double wooden doors. Inside, a long nave with a pale blue-white barrel vault is crossed by a dark brick arch on square piers, and plain wooden pews line the central aisle.

Franciscan monks founded the school in 1536 to teach sons of indigenous noble families in European subjects. It became the first center of higher education on the American continent before being damaged by earthquakes and political changes over the centuries.

The college's name, Santa Cruz, was chosen for the feast of the Epiphany, January 6, 1536, when it opened; the date was meant to echo the calling of the gentiles to the faith. Students were taught Nahuatl, Spanish and Latin, and the trilingual pupils helped Bernardino de Sahagún gather testimony from Aztec elders for the Florentine Codex. The Nahua botanist Martín de la Cruz, trained here, wrote the illustrated herbal Libellus de Medicinalibus Indorum Herbis.

Plaza de las Tres Culturas is the starting point for a visit, and public transportation from downtown Mexico City brings visitors nearby. Guided tours are available to explore the interiors, which are not always freely accessible.

The Colegio opened on 6 January 1536, the feast of the Epiphany, a date chosen to echo the calling of the gentiles to the faith. Viceroy Antonio de Mendoza, Bishop Juan de Zumárraga and Audiencia president Sebastián Ramírez de Fuenleal attended the opening Mass, after which Zumárraga hosted a banquet for the first pupils.