While still working at YPF, Calderón became acquainted with the mathematicians at the University of Buenos Aires: Julio Rey Pastor, the first Professor in the Institute of Mathematics, his Assistant Alberto González Domínguez (who became his mentor and friend), Luis Santaló and Manuel Balanzat.
The collaboration begun by Zygmund and Calderón in 1948 reached fruition in the Calderón-Zygmund Theory of Singular Integrals and lasted more than three decades.