The Test in Turin on Saturday (Sunday AEDT) marks the end of the November tour for New Zealand, who edged England and Ireland in their opening two matches but lost 30-29 to France in Paris last weekend.
The veteran pair of Cane and Perenara are moving to Japan to play club rugby.
Cane, who has 103 caps, will line up on the open side of the scrum in a switch to the loose trio with Samipeni Finau out with concussion. Ardie Savea moves back to No. 8 with Wallace Sititi now on the blindside.
Perenara, with 88 caps, has been named as replacement halfback and will surely get a run out to mark the end of his All Blacks career.
New Zealand coach Scott Robertson had been expected to ring the changes and give opportunities to several fringe players but has put out a strong side against Italy, who lost heavily to Argentina in their opening November international and had a struggle to get the better of Georgia last week.
There are a total of five changes in the All Blacks line-up from the narrow loss in Paris last Saturday.
Loosehead prop Ethan de Groot, not used since being suspended for breaching team protocol ahead of the first Test on tour against England, has been chosen in place of Tamaiti Williams, who suffered a neck injury against France last Saturday, while Patrick Tuipulotu replaces Tupou Vaa'i in the second row.
Jordie Barrett, who was set to have a scan on his knee, is replaced by the experienced Anton Lienert-Brown, while Mark Tele'a is back on the right wing after a hand injury, replacing Sevu Reece in the two backline changes.
"This Italy team has made a real impact on the international stage this year, with a strong showing in the Six Nations," Robertson said in a statement naming the team.
"We know the passion this team will bring, so we are preparing for a physical and motivated Italy for our final test of the tour."
Team:
15-Will Jordan, 14-Mark Tele'a, 13-Rieko Ioane, 12-Anton Lienert-Brown, 11-Caleb Clarke, 10-Beauden Barrett, 9-Cam Roigard, 8-Ardie Savea, 7-Sam Cane, 6-Wallace Sititi, 5-Patrick Tuipulotu, 4-Scott Barrett (capt), 3-Tyrel Lomax, 2-Codie Taylor, 1-Ethan de Groot
Replacements: 16-Asafo Aumua, 17-Ofa Tu'ungafasi, 18-Fletcher Newell, 19-Tupou Vaa'i, 20-Peter Lakai, 21-TJ Perenara, 22-David Havili, 23-Damian McKenzie.
