Atletico lost at Madrid 3-0 in the opening leg of their Champions League semifinal on Tuesday.
Soldado barely missed with a header on the other end before Neymar helped Messi reach the 50-goal mark for the fifth time in his career.
For all the great work done to revive a sleeping giant in Atletico by Diego Simeone over the past five-and-a-half years, ending their hex against Real in the Champions League continues to allude them. "You can defend well, you can control the midfield, but you still need someone to score the goals".
Real Madrid superstar scored his 400th goal for the club and that too in style.
But the forward will not be able to reach the milestone in their next match against Granada after Zinedine Zidane has chose to give his talisman a rest.
Former Manchester United player Phil Neville was at the Bernabeu to witness Cristiano Ronaldo, his former team-mate, scoring a hat-trick for Real Madrid in their 3-0 Champions League semi-final first-leg win over Atletico Madrid.
"I don't know whether it's all down to him being rested", said Zidane. I said yeah, I'd like to, that if I had to leave I would nearly certainly go to London, but that I didn't know what Madrid would do. Neville states he no longer works as a sole winger, rather he plays a more central role as a makeshift number 9, in order to be more available in the bow for attacks.
Ronaldo had scored only two goals in his first eight games in the European competition.
Villarreal is five points behind fourth-place Sevilla, the last team now securing a Champions League spot. Could Granada spoil Real's championship hopes on their way out of the league? "We had one more midfielder than our rivals. Rafa has felt something, not very much, but as always we do not want to take risks with someone who has an issue".
That makes it a bad time for them to come up against a side who have proven incredibly hard to beat this season, with Villarreal losing just one of their seven clashes with top-four sides this season.
Vazquez saw his effort come back off the crossbar before Casemiro then sent a close-range effort over an open goal after the forward had a shot blocked when played in by Mateo Kovacic.