Manchester United face Manchester City in a top-of-the-table clash at Old Trafford tomorrow (4.30pm).
City go into the game in red-hot form and are undefeated in 15 Premier League games.
United have turned on the style again in recent weeks, with the 3-1 victory over Arsenal exemplifying this, but they trail City by eight points in the table.
The Red Devils will miss Paul Pogba, who is serving a three-match suspension after he was sent off for his ferocious challenge on Hector Bellerin last weekend at the Emirates.
And Neville believes Mourinho hasn’t just got the problem of who to replace Pogba with.
“The biggest selection dilemma for Jose Mourinho, apart from who replaces Paul [Pogba], is whether he will go three at the back,” Neville told Sky Sports’ The Debate.
“City will have three up front and they normally have two wide men in Raheem Sterling and Sane.
“Aguero and Jesus are likely to play up front. So does he go three central defenders and Valencia and Young. That’s five vs three, so United will be outnumbered in midfield.
“Does he gamble and play four at back or change system and maybe bring in Luke Shaw and play in a conventional big four?
“So that’s the biggest conundrum for Jose to go with a back five or a back four.”
City will have fond memories of previous visits to Old Trafford and won 2-1 there last season in the league.