Cano put on a prodigious display at the plate earlier this year against the surging Indians heading into Monday's makeup doubleheader in Cleveland.
New York (23-13) enters on a season-high five-game win streak while Cleveland (20-15) has won four straight at home and eight of nine there heading into these contests that were rescheduled when a four-game series last month was cut in half due to bad weather.
The Yankees won the two games by a combined 25-7 behind Cano, who was 7 for 10 with three homers, seven RBIs and six runs scored. He is 26 for 53 (.491) with five homers and 14 RBIs during a 13-game hitting streak against the Indians.
Cano is 8 for 19 against Justin Masterson (5-2, 3.67 ERA), who will start the opener. He has never faced Game 2 starter Trevor Bauer (1-1, 2.70).
Yankees manager Joe Girardi said Cano will play both games, but just once at second base. Vernon Wells will play once in the outfield while catchers Chris Stewart and Austin Romine each will start once.
"I believe we're seeing Masterson first ... so my plan is not to play Robbie Cano both games in the field, DH him probably one game," Girardi said.
Wells went 4 for 8 against Cleveland in the two April meetings while Brett Gardner was 5 for 10 with three RBIs and three runs scored.
Masterson is 3-2 with a 2.56 ERA in six starts against the Yankees, and he's limited Wells to two hits in 18 at-bats.
Fellow right-hander Bauer will make his seventh career start and third of the season. He has limited batters to a .097 average but has walked 13 over 10 innings in 2013.
The Indians are a major league-best 11-2 since April 29 after taking two of three in Detroit this weekend. They came from one run down in the ninth Sunday in a 4-3, 10-inning victory to pull even with the Tigers atop the AL Central.
"That was as good a team effort as you are ever going to see,'' manager Terry Francona said.
Girardi was echoing a similar theme after his injury-plagued Yankees completed a weekend sweep in Kansas City with Sunday's 4-2 victory. Cano delivered a two-run homer.
"These guys have gotten it done, different ways, different guys every night," Girardi said.
David Phelps (1-1, 5.02) will make his third 2013 start in the opener for New York after getting no decisions in the first two. The right-hander has never faced Cleveland.
Left-hander Vidal Nuno will make his first major league start in Game 2. Nuno pitched three scoreless innings in his lone big-league appearance April 29 against Houston.
These teams excel in tight games, with the Yankees 7-1 in one-run contests and the Indians 9-3.