Shortly after John lost the 2004 election, the Edwards family was tested again. Elizabeth was diagnosed with breast cancer, but with the support of her husband and family, she vowed to beat it.

Oprah says the title of Elizabeth's new book, Resilience, perfectly describes Elizabeth's life. After surviving the death of a child and overcoming her first bout with breast cancer, Elizabeth was hit with another devastating blow.

On December 28, 2006—two days after John announced that he was joining the 2008 presidential race—Elizabeth says her husband of 29 years told her he'd broken the promise he made on their wedding day. He had been unfaithful.

While sitting with Oprah in the dream home she and John built together, Elizabeth speaks publicly about that night for the first time.

Oprah: The first time you were told, I read in Resilience, you got physically sick.

Elizabeth: I did.

Oprah: You cried, you screamed, you cried.

Elizabeth: And then I threw up. That was a really tough night.

That night, Elizabeth says John told her the other woman, whom Oprah agrees not to mention by name, was out of his life. "[He said] he had regretted what he had done and this was only one time, which was still, you know, that still leveled me," she says.

Then, Elizabeth says she asked John to drop out of the presidential race.

"I knew there would be people who would be following him around. [People] would be trying to uncover things," she says. "So I thought for my family, for my children, for John, for me, that it would be best if he got out of the campaign. He said, and truthfully he was right, it was hard to argue with this, 'If you want to raise a lot of questions, what you do is get out of a campaign you got in two days before.'"

While John campaigned across the country, Elizabeth, the woman who'd stood by his side for so many years, took a step back.

At first, Elizabeth says she canceled speaking engagements because she simply couldn't go through with them.

"It would just be sort of overwhelming," she says. "I was still angry and hurt and had a lot of self-doubt about who I was and what I meant to him. You know, all those things that I think women in my position go through."

Despite their efforts to keep the affair a secret, rumors about John's relationship with a woman who worked on his campaign began swirling in the media. Publicly, John dismissed the reports and denied having an extramarital affair.

On January 30, 2008, he dropped out of the presidential race.

Months later, the truth finally came out. As millions watched, John admitted during a Nightline interview to cheating on Elizabeth. "Let me say this, and I want to say it absolutely clearly. I was wrong, and I am responsible," John said.

At this time, Elizabeth was struggling with another admission. A year and a half after John told Elizabeth about his one-time indiscretion, she says she learned the whole truth.

John told her he'd cheated more than once. In fact, the affair had lasted for months.

"It felt like a blow to me," Elizabeth says. "It was so hard for me to even imagine such a thing, and then, his telling me that it had happened more than once. That was probably the worst…they compete for the worst moment because [of] all the work we'd done, all the trust we'd tried to build."

To try to make sense of John's betrayal, Elizabeth says she's asked him how it started. By his account, the affair began with just four words—"You are so hot."

Watch as Elizabeth recounts the start of John's affair.  

While on a business trip, John told Elizabeth he met the other woman at his hotel. "What John had said is that this woman had spotted him in the hotel," she says. "John had gone to dinner at a nearby restaurant, and then he had walked back to the hotel. When he had walked back, she was standing in front of the hotel and said to him, 'You are so hot.'"

In Resilience, Elizabeth says she would have wagered her home on the fact that John, her husband of 28 years at the time, would never have responded to this sort of come-on. "I don't think he knows to this day why he said yes," she says.

Like many women in her situation, Elizabeth says she wanted to know the details of her husband's affair. "I'm a puzzle-doer," she says. "I had pieces of the puzzle, and I felt like it was going to make sense if I had all the pieces."

Oprah: Is the first thing you wanted to know is, "Do you love her?"

Elizabeth: I'm sure that I asked that, but it seemed impossible to me, and I think, impossible to him. This is a person very, very different from me and really very different from him.

To this day, Elizabeth says she and John don't really know why he cheated. "He really has tried, I think, to figure it out, and to talk to people and try to work that out, but I don't think he really knows," she says. "I mean, it was opportunity and didn't seem like there were any consequences."

Elizabeth says she encountered the other woman once at a political rally in Chapel Hill. "I didn't meet her really. One time, we were in the same place," she says. "I was with my family and children and my brother and sister, and she walked by into another area. … And that's the extent."

At first, Elizabeth says she wondered if she did something to cause the affair, but she's come to the conclusion that it was never about her. Now, she holds John and the other woman responsible.

"I blame John, but also, women need to have more respect for other women," she says. "It takes a lot of work to put together a marriage, to put together a family and a home. … You have to have enough respect for other human beings to leave their lives alone. If you admire that life, build it for yourself. Don't just try to come in and take somebody else's life." Oprah Winfrey reporting.

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