Amorim has previously said not even the Pope could convince him to move away from the back three which proved so successful at Sporting CP.
But after losing Amad Diallo, Bryan Mbeumo and Noussair Mazraoui to AFCON, the Portuguese coach has hinted that he might be forced into a change of style.
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United have been using training sessions to try out different systems after more than a year of Amorim sticking rigidly to his tried and tested 3-4-3.
"It will depend on the way we play that particular week," Amorim said, when asked about how he will cope with the loss of Amad, Mbeumo and Mazraoui for up to a month.
"But if we have to change to a four back four, we change four back four.
"I'm just focused on the next game. Let's go step by step.
"We have a big match [against Aston Villa]. We need to win. We need to try to find different ways of playing, especially without Amad and Bryan. We lost some characteristics that are hard to find."
As well as missing Amad, Mbeumo and Mazraoui against Villa, Amorim will also be without Casemiro after he picked up his fifth yellow card of the season in the 4-4 draw with Bournemouth.
It could present an opportunity for Kobbie Mainoo to make his first Premier League start since May.
On Monday at Old Trafford, Mainoo's half-brother, Jordan Mainoo-Hames, was pictured wearing a "Free Kobbie Mainoo" T-shirt -- a reference to the midfielder's lack of game-time this season.
In response, Amorim said he wants to "avoid nonsense and noise," but opened the door for Mainoo to play a part at Villa Park on Sunday.
"He's responsible for his acts and his act was to play well in the last game, I'm just focused on that," Amorim said.
"I had the situation in Sporting that my brother wrote something on the internet, and I have to answer for that. My explanation is that he has his life, he has his opinion, and it's nothing to do with me. So I will do the same with Kobbie.
"Kobbie needs to fight for his job. I think that it is not a bad thing to be on the bench of Manchester United when you are 20-years-old.
"I remember [Cristiano] Ronaldo was on the bench, [Wayne] Rooney was on the bench sometimes. [Juan] Veron was not playing. I remember all the history of Manchester United and this [the club] didn't fall.
"Maybe the next game, Sunday, he is going to start.
"So let's continue trying to avoid the nonsense and the noise. I just want to help the team to win and help Kobbie to be a better player."
