Max Evans switches to the wing for the match in Rome to accommodate De Luca at outside center and replace the injured Lee Jones.
Scotland coach Andy Robinson named an otherwise unchanged team for a match that will decide which country finishes last with the so-called wooden spoon.
"Nick was unfortunate to miss the game in Ireland through a hamstring problem and the challenge for him on Saturday will be to contribute as purposefully against the Italians as he did in his last game, against France," Robinson said.
Robinson also called up Jack Cuthbert, who can play fullback or wing, to the bench for what could be a first appearance in the Six Nations and just a second cap overall.
"He's strong and we know from his involvement with the squad back in the summer how much it means to him to play for Scotland," Robinson said.
After four defeats, Scotland leads last-place Italy only on points difference. The Scots have won only twice at Italy since the Italians were admitted to the tournament in 2000.
