Zinedine Zidane has opted for Isco in his starting line-up to face Atlético Madrid in the Champions League semi-final first leg at the Bernabéu.
Diego Simeone, meanwhile, has negotiated his shortage of recognised right backs by playing Lucas Hernández in that position.
Real Madrid go for Isco
Isco's superb showing in the recent La Liga match away at Deportivo La Coruña, which Madrid won 2-6, has ostensibly convinced Zidane that he deserves to start the match in the absence of Gareth Bale.
Varane has returned from injury without any hiccups, and will partner Sergio Ramos in the heart of defence.
Real Madrid XI: Navas; Carvajal, Varane, Ramos, Marcelo; Modric, Casemiro, Kroos; Isco, Cristiano, Benzema.
Lucas fills in for Atléti
'El Cholo' Simeone faced a selection dilemma in the run-up to the match, with both of the club's right backs, Juanfran and Šime Vrsaljko, out through injury. José Giménez has been filling in on the right side of the defence, but he has also been consigned to the treatment table.
In the absence of other options, Simeone has selected Lucas Hernández to fill that gap.
In attack, Gameiro will partner fellow Frenchman Antoine Griezmann.