The Portugal international meets the Rojiblanco again, for the first time in United colours, after facing them 35 times in all competitions, and coming out on top on 17 occasions.
These include Real Madrid's two Champions League final triumphs over their neighbours and the hat-trick that overturned Juventus' two-goal first-leg deficit in the 2018/19 quarter-finals.
He bagged trebles at both the Vicente Calderon and the Wanda Metropolitano and also hit three in a last-four Champions League tie at the Bernabeu in 2017.
Little wonder that the Atleti supporters will give him a hostile reception when he is back in Madrid for Wednesday night's round-of-16 encounter.