FA Cup giant-killers Plymouth Argyle drew Premier League champions Manchester City on Monday as the second tier side's fifth round reward for a shock defeat of Liverpool on Sunday.
Holders Manchester United will host Fulham at Old Trafford in one of at least three all-Premier League clashes, with League Cup finalists Newcastle United at home to top tier rivals Brighton & Hove Albion.
Bournemouth will host Wolverhampton Wanderers in another all top flight encounter.
Struggling Plymouth caused one of the great upsets of the FA Cup on Sunday when they beat a second-string Liverpool 1-0, ending the Premier League leaders' hopes of a quartet of trophies this season.
The Pilgrims are bottom of the Championship but City, who reached the fifth round with a 2-1 win at third tier Leyton Orient on Saturday after going behind early on, have been misfiring this season.
There will be a fourth all-Premier League clash if Nottingham Forest avoid trouble at League One (third tier) Exeter City on Tuesday, with Ipswich Town awaiting the winners.
Aston Villa, who ended Tottenham Hotspur's hopes on Sunday, host second tier Cardiff City.
The fifth round matches will be played on the weekend of March 1 and 2.
Last 16 draw in full
Preston North End v Burnley
Aston Villa v Cardiff City
Crystal Palace v Millwall
Manchester United v Fulham
Newcastle United v Brighton & Hove Albion
Bournemouth v Wolverhampton Wanderers
Manchester City v Plymouth Argyle
Exeter City or Nottingham Forest v Ipswich Town
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