This one features one starter who hasn't pitched in 11 days and another who owns baseball's worst home ERA.
Brandon Workman returns from suspension for the Red Sox as they visit the Bronx to open a three-game set Friday night against struggling Yankees starter Vidal Nuno.
New York (40-37) took five of seven from Boston in April as these ancient rivals reunite with both coming off needed wins.
The Yankees avoided a season-worst fifth straight loss Wednesday with a 5-3 win at Toronto. They improved to 5-4 in a 15-game stretch within AL East play.
"Within the division, the games that we've played, we've played six against Toronto and three against Baltimore and now we're going to play Boston and Tampa," manager Joe Girardi said. "I thought we needed to play a good game before the off day."
Boston (36-43) improved to 2-5 on a 10-game trip with Wednesday's 5-4 victory at Seattle. David Ortiz homered and drove in three runs and Clay Buchholz won in his return after being sidelined a month with a knee injury despite allowing three home runs.
Neither of Friday's starters has started in this longstanding rivalry.
Workman (1-0, 2.88 ERA) last pitched June 15, allowing two runs over six-plus innings in a 3-2, 11-inning loss to Cleveland. He is back after serving a six-game suspension for throwing near the head of Tampa Bay's Evan Longoria and getting ejected on May 30.
The right-hander has limited opponents to a .190 average in five starts, and held the Yankees to a .167 mark over 3 1-3 innings in four relief appearances last season.
Nuno (1-4, 5.88) is 0-3 at home over eight appearances - seven starts - with a 7.09 ERA. He has surrendered five homers and 13 runs over 9 1-3 innings in consecutive losses, giving up three homers and five runs in 6 1-3 innings in Saturday's 6-1 defeat to Baltimore.
The left-hander has allowed a major league-worst 13 homers at home. With injuries to Michael Pineda and CC Sabathia, the Yankees have no choice but to keep Nuno in the starting rotation.
''This is what we have. And as I said, it's not like there's just starting pitchers lying around out there,'' Girardi said. ''Right now, this is what it is.''
Carlos Beltran leads New York with three homers in the season series and is tied with former Boston star Jacoby Ellsbury for the team lead with six RBIs. Derek Jeter, who turned 40 on Thursday, is 7 for 21 versus the Red Sox.
The Yankees have done a good job in limiting Ortiz to a .227 average in the season series and Dustin Pedroia to a .154 mark. Ortiz needs three extra-base hits to become the 36th player with at least 1,000 for his career.
New York's Mark Teixeira has homered in three of his last five games with a two-run shot Wednesday.
"He's an RBI guy, he's an RBI machine," Girardi said. "He's important to our lineup and we missed him dearly last year. The big thing is that we keep him out there and we keep him going."