Lester will supplant struggling right-hander Julian Tavarez in the Boston rotation by kicking off a four-game series at Jacobs Field against the Indians. To make room for Lester on the roster, the Red Sox will designate Joel Pineiro for assignment on Tuesday, effectively ending the right-handed reliever's inconsistent first season in Boston.
As for Lester, the 23-year-old left-hander last pitched in the Major Leagues on Aug. 23, 2006.
"I'm excited and ready to go," Lester said from Pawtucket, R.I., where he did a workout in the afternoon before re-joining his teammates in Boston for the Sunday evening flight to Cleveland.
After undergoing six chemotherapy treatments, Lester was declared cancer-free in December. The Red Sox, respecting what he had gone through, brought Lester along slowly in Spring Training and let him pitch in the Minor Leagues for the first three and a half months of this season.
"There's a lot of excitement," Lester said. "It will be a little surreal, but I'm going to enjoy it."
So will his teammates, his manager and the entire Red Sox organization.
"He's healthy. He's been through a lot. I'm sure it's going to be an emotional day for his family and for us," said Red Sox right-hander Curt Schilling. "He's part of the family. To see him go through what he went through and to come out on top, it's going to be exciting."
"You know, we want to win games so bad. But I can't sit here and tell you there won't be some emotion involved when he gets to take the mound," said Red Sox manager Terry Francona. "I think his folks are going to be there, which, I'm sure for them will be extra special. I think, talking to Jon, he just wants to win the game."
Meanwhile, Tavarez, who is 5-8 with a 5.27 ERA in 18 starts, was available out of the bullpen for Sunday's game against the White Sox. In his last five starts, Tavarez was 0-4 with a 7.71 ERA.
The rubber-armed righty has been a reliever most of his career.
"Even with the recent struggles, his first time through the order has actually been almost dominant," said Francona. "That second time through hasn't been so good. We'll get him out in the bullpen. He's stretched out. He still feels good about himself. This has got a chance to really help our bullpen. He's the guy that can throw whenever you want, and if he's pitching with success, it gives us that other arm out there."
Lester's only setback during his comeback was in May, when he developed some cramping in his left forearm and was shut down for a couple of weeks.
He's made 17 starts in the Minor Leagues this season, 14 which have come at Triple-A Pawtucket. Lester is 4-5 with a 3.61 ERA over 84 and 2/3 innings. Lester has held opponents to a .247 average.
Lester's initial reaction when Francona informed him of the news?
"Little of a businessman-like approach," said Lester. "It really hasn't sunk in yet, but I'm sure it will [Sunday night and Monday], for sure. I'm looking at it as another start right now, and hopefully don't get too nervous come [Monday]."
A recent conversation that Francona and pitching coach John Farrell held with Pawtucket manager Ron Johnson played a role in the timing of Lester's recall.
"I think the clincher is probably when I don't know if John Farrell or myself said [to Johnson], 'If we're 100 percent and don't need Lester, should Lester be here?' And [Johnson] goes, 'Yes.' That kind of clinches it for us," Francona said.
Last year, Lester was promoted to Boston in June and took a regular turn in the Boston rotation for more than two months, going 7-2 with a 4.76 ERA. For several years, he has been regarded as one of the top left-handed pitching prospects in the Major Leagues.
The Red Sox were determined not to bring Lester back too early.
"We've been staying up on this kid, I think, it's pretty evident, all year," said Francona. "Where we thought he was, what needed to happen, what's best for him, what's best for us. I think we got to a point where we thought this might be in his best interest and ours. It will be interesting to see how he does. We're excited. We've had a lot of conversations with a lot of people trying to do the right thing."
As much as the Red Sox were jarred last season when they got the word of Lester's cancer diagnosis, they were just as thrilled to hear he's back.
"He's definitely an inspiration to all of us," said Red Sox closer Jonathan Papelbon. "We go through ups and downs in life and he went through a really big down in life and was able to fight through and come back and hopefully help us win a World Series."
In typical Lester fashion, he downplayed the courage he showed in coming back from cancer.
"I don't know about inspiration," Lester said. "I did what everyone else would have done in that situation. I want to come back and play baseball. I love to do this; this is my job. I just want to come back and be with these guys and do this for a long time."
The Red Sox feel he has just the make-up to do so.
"He's not a typical 23-year-old," Francona said. "He was ready to pitch. Very business-like. I don't mean that in a bad way. He's always real personable. But he was like, 'OK, I'm ready to go. Tell me when to be there and what to do and I'll be there.'"
Lester, who gave up seven hits and three runs in his most recent start, feels ready. He left no doubt about that.
"I feel physically good," said Lester. "Mentally, I feel good. After my last start, things are starting to come around."
It has been a long road back for Lester, but the reward for his perseverance is about to come.
"The constant battle of getting pushed back, the pitch counts, all that -- it's been hard. But you have to sit back and see that they have your best interest involved, and they want you to be healthy," Lester said. "It's been hard getting treated like you're in a glass bottle, so it'd be nice to finally break through and get to go pitch again."
It's likely Lester won't be the only uniformed player with a few goosebumps on Monday night.
"It's going to be a pretty surreal moment after all he's gone through and battled through," said Papelbon. "The kid pitching in Major League games again is a situation where that's pretty unbelievable. It's going to be a pretty neat little feeling, I'll guarantee you that."
Ian Browne is a reporter for MLB.com. Brendan McGair, a contributor to MLB.com, contributed to this report. This story was not subject to the approval of Major League Baseball or its clubs.