The veteran, acquired by the Astros from the Baltimore Orioles in a trade deadline deal, faced an uncertain future in baseball -- and in life -- just two years ago.
Editor's note: The above video aired when Mancini joined the Astros.
It started during Spring Training in 2020 when Mancini said he was struggling because he felt so sluggish.
"I’d take BP, and I’d just get tired after a few swings. So I knew something was up, but I chalked it up to just getting older," Mancini posted on The Player’s Tribune.
After his annual team physical, doctors said his iron levels were low. They thought he might have an ulcer or celiac disease, Mancini said, so they did a colonoscopy.
Mancini woke up to an unexpected gut punch.
"He said he found a tumor on the, you know, right side of my colon and I that I was going to have to go get a CAT scan immediately to see if the cancer had traveled anywhere else in my body." he shared in a Twitter post.
"Obviously, nothing can truly prepare you for a cancer diagnosis when you're in your 20s but I tried to use lessons I've learned from baseball."
The next big step was surgery to determine if he'd need chemotherapy. When Mancini woke up in the recovery room, he learned that Major League Baseball had shut down because of the COVID quarantine.
Six days later, on his 28th birthday, the doctors at John Hopkins Hospital delivered the news that he didn't want to hear.
"Three of my 23 lymph nodes had tested positive for cancer and that I was gonna need chemotherapy."
Mancini said six months of chemo during COVID was tough. He admitted he had some "why me?" moments but credited his family, girlfriend Sara Perlman and the Orioles with getting him through the darkest days.
“There were times early on when I wasn’t entirely sure I’d be playing baseball again,” Mancini told mlb.com. “I'd be lying if I'd say that was the first thing that came to mind. The whole time I just wanted to be healthy long-term and live a long life. And baseball definitely was on the back burner when I was going through all that.”
"I couldn't control that I had cancer, I couldn't control the fact that I needed to do chemotherapy. You just gotta wear it sometimes and get up that day and attack it," Mancini said.
And that's what he did -- on and off the field.
Mancini returned to the Orioles the next season and won the 2021 AL Comeback Player of the Year Award.
When he returned to Camden Yards last month as a Houston Astro, Orioles fans welcomed him back with a rousing standing ovation.
As the Astros DH, Mancini has made some clutch hits on their road to the American League Championship, including his first career grand slam a few days after he joined the team.
This will be his first World Series and he's soaking it all in with more appreciation -- and perspective -- than most.
"Between COVID and chemotherapy, it was a lot, but we're all gonna face adversity throughout our lives and you can cower in the face of tough times or you can battle it head-on and make yourself better from it."