It'll be a big start for a lot of cancer survivors across the country as well as plenty of others who are fighting the terrible disease along with their friends and families. For that matter, it's a breakthrough point in Lester's career on so many levels.
"The beauty of it," teammate Curt Schilling said, "is that Game 4 of the World Series is going to be a whole lot different than had he not gone through what he went through. There's no mountain he can't climb, no hurdle he can't jump. It's a challenge for a young pitcher, but at the end of the day, there's nothing he's going to see in Game 4 that ... isn't dwarfed by what he's already beaten and overcome."
Still, that's not what Lester wants to have on his mind when he takes the mound on Sunday evening. He'll have enough on his mind without thinking about the extra significance.
"I just want to be treated like a normal pitcher and go out there and pitch," Lester said on Friday. "That's what I've tried to do."
To the Red Sox and manager Terry Francona, that's what Lester is, which says plenty about how far he has come.
When Tim Wakefield was deemed unavailable for the World Series due to his lingering right shoulder issues, Lester was Boston's best option to plug into the rotation. He tossed five quality outings in 11 starts from late July through September, including three in a four-start stretch in early September. He made the playoff roster over proven postseason pitcher Julian Tavarez as an extra arm in the bullpen.
"The last six weeks or so," Francona said, "the ball is really starting to come out of his hand like the reports we got in '05."
Considering Lester was once mentioned in the same sentence with Jonathan Papelbon among Boston's top pitching prospects, that's a form the Red Sox would love to see.
It's not a matter of Lester feeling physically stronger, he said. It's more a matter of regaining his polish and his arm strength. Like any major injury that costs a pitcher a lot of playing time, it takes time to get back to pre-injury form.
"I'm lifting the same weights, doing the same things and [I] feel good about it," Lester said on Saturday. "It's just right now, it seems like my fastball has got a little extra on it. It's getting the life back to it. I'm not getting as tired toward the end of the game. Just little things. My mechanics are repeating themselves more, and [I'm] just being more consistent in the [strike] zone."
Yet there's a mental side to Lester's comeback that will never be the same as before the injury, and he's stronger for it.
Lester has always been an intense competitor. It's how he got to this point in his career, and it's no small reason why he was able to come back from his condition without falling into self-pity. However, there was a side to that competitiveness that could work against him, a perfectionist tendency that could eat him up.
It was a feeling Lester had for most of his rookie season in 2006, and he admits it never really allowed him to soak in where he was and what he was doing.
"Definitely," Lester said on Saturday. "Last year, I didn't really get a chance to enjoy what was going on, and being up in the big leagues, being a part of every kid's dream and playing up there with these guys. I took a lot of things for granted last year, and I beat myself up over little things."
It's not just a figure of speech with Lester. It was real.
"Last year, I threw a ball the second pitch of the game," Lester recalled on Friday, "and it was like, 'Game over.' I'd beat myself up because I didn't throw strikes. This year's a lot more relaxed, and I don't beat myself up too much. I just try to go out there and pitch and do what I can."
That's what perspective does, and it reflects in his game.
"Jon has a way, as a lot of young pitchers do, of kind of maybe working himself into trouble," Francona said. "What's sort of special about him is, he has a way of working himself out of trouble."
Lester allowed a .283 batting average with runners in scoring position during the regular season. When the bases were loaded, however, opponents went 0-for-7 with two sacrifice flies and two runs scored.
Compared with what Lester was doing this time last year, bases-loaded situations just don't seem that bad. But compared to what so many other patients with cancer endure, Lester doesn't think his situation was anything special. He doesn't have magical words for anyone on how to handle the treatment, the stress or the uncertainty.
The best way he can give hope is to simply pitch. And be normal.
"I think that if people would have been in my situation, they would've done the same thing," Lester said. "So I don't think that I'm any different than anybody else. It just so happens that I play baseball, and we're in the World Series and we're on a big stage.
"You know, it's great if I am [an inspiration]. Hopefully, I can help somebody out. But I don't look at it that way. I just look at it as, I was a normal person and did anything that anybody else would've done."
Lester would love to look at Sunday the same way. So would his team.
"I thought he was a very grounded young man before this all happened," Francona said. "Now that he has gone through what he has, I think it's even more."