The 26-year-old Cardiff fly-half is one of four changes in the Wales team to face France at the Stade de France.
But instead of taking his place at number 10, where he has won the lion's share of his 14 caps to date, the former rugby league stand-off will take over from Tom Shanklin at inside-centre as coach Steve Hansen aims to take on the French at their own game.
Hansen said: "I suppose it is very much horses for courses in certain positions although in the cases of Mark (Jones) and Humph, we didn't have any choice.
"As far as Iestyn is concerned, I think he will enjoy the opportunity and we are looking forward to seeing him playing that role alongside Mark Taylor and outside Stephen Jones.
"It certainly doesn't reflect badly on Tom Shanklin or Gareth Cooper, both players have performed very well this season.
"It is just a case of having a look at others and choosing the players who we feel will be best suited for the game.
"Iestyn has grown as a player over the past few months and he has a great deal to offer.
"We did think about him at number 10 but we believe that the fly-half position is where the main operator plays. Considering Iestyn's background - in rugby league - we think he is best suited to playing at centre. It is nothing more than that."