Holders Manchester United and arch-rivals Arsenal were kept apart when the draw for the semifinals of the FA Cup was made in London on Monday.
United were paired away with Newcastle, with Arsenal up against Blackburn Rovers.
That left open the prospect of an Arsenal-Manchester United final, with the FA Cup representing both English giants' last chance of silverware this season after they were each knocked out of the Champions League last week.
League Cup winners Chelsea, beaten by Newcastle in the FA Cup, lead the Premiership by eight points from United with Arsenal two points further behind in third place.
United, who have won the FA Cup a record 11 times, reached the last four with a 4-0 thrashing of Premiership strugglers Southampton on Saturday with Arsenal, nine-times Cup winners, beating Bolton 1-0.
Sunday saw Blackburn and Newcastle, who have each won the Cup six times, enjoy 1-0 quarterfinal wins over Leicester and Tottenham, respectively.
The Newcastle-United semi will see Alex Ferguson's men trying to frustrate what is set to be Alan Shearer's last bid for a trophy.
Newcastle captain and former England striker Shearer has vowed to retire at the end of the season, and he now comes up against the club who wanted to sign him earlier in his career.
Shearer turned down the chance to play for United and has yet to win any trophy since joining Newcastle in a US$23 million deal from Blackburn in 1996.
Newcastle will be looking to make it eight wins in a row when they face Olympiakos in a bid to cement their place in the UEFA Cup quarterfinals on Wednesday and Shearer said: "We are in the semifinal and we deserve to be there, but we have not achieved anything.
"We have got one foot in the quarterfinals of the UEFA Cup, we are in the semifinals of the FA Cup. These are interesting times now and everyone has got to stand up and be counted," he said.
Shearer was a member of the Newcastle teams beaten by Arsenal and then Manchester United in the 1998 and 1999 FA Cup finals at Wembley, before experiencing more FA Cup heartbreak at the London venue when beaten there by Chelsea in the 2000 semifinal.
It is now 50 years since Newcastle last won the FA Cup and Shearer said: "I hope Cardiff is more friendly to us than Wembley has been over the years.
"I said before the competition started that if you want to win it, it is inevitable that you are going to have to play one of the big teams in the final, one of the big three, and I still think that is the case," he said.
Blackburn, seven points above the relegation zone, and Arsenal will be involved in a dress rehearsal for their Cup clash when they meet in the Premiership at Ewood Park on Saturday. Rovers striker Paul Dickov is set to be up against his old club after scoring the vital penalty against Leicester.
Were Rovers, now managed by Mark Hughes -- a four-time FA Cup winner as a player -- and Newcastle to meet in the final, the spotlight would fall on Graeme Souness.
The Scot quit as Rovers manager earlier in the season to succeed Bobby Robson as Newcastle boss, the Liverpool midfield great making it clear he thought he was moving to a bigger club.
Arsenal are 11/8 favorites with leading British bookmaker Ladbrokes, United 6/4, Newcastle 5/1 and Blackburn 7/1.
"We've never felt so wanted as we have in the last 24 hours. Everybody wanted us, but we're going to show everybody that if Arsenal take us lightly then we're well prepared and they'll come a cropper," Rovers assistant manager Mark Bowen said jokingly.