The Associated Press reports that Lopes was the only fatality in a car accident involving seven people Thursday night outside the city of Jutiapa, 150 miles north of Tegucigalpa, the Honduran capital.
"The car rolled for reasons that we still don't know, and that are being investigated," police spokesman Luis Aguilar told the AP.
It's not known whether she was wearing a seatbelt. The other six people in the car were taken to a nearby hospital.
Rob Goldstone, a publicist for TLC, said the singer frequently traveled to Honduras where she kept a condo, having first fallen in love with the country after visiting there in the aftermath of Hurricane Mitchell, which killed thousands of people in 1998 and devastated the region's economy.
Lopes was lending a hand at a child welfare center in the city of La Ceiba. It's believed her companions riding in the car also worked there.
"It was a favorite vacation spot of hers and she would go there for a few weeks at a time," Goldstone said. "She was out there this time with some friends...and did help out and volunteer with a lot of children's welfare center in Honduras."
Reaction to Lopes' tragic death was swift Friday morning.
"No words can possibly express the sorrow and sadness I feel for this most devastating loss," said Arista president L.A. Reid, who helped elevate TLC to one of the best-selling female groups of all time. "Lisa was not only a gifted and talented musical inspiration, but more importantly, she was like a daughter to me.
"My thoughts and prayers are with Lisa's family and friends. Her legacy will be remembered forever."
TLC, which was made up of Lopes, Rozonda "Chilli" Thomas and Tionne "T-Boz" Watkins, took the music world by storm with such hits as "Waterfalls," "No Scrubs," and "Unpretty." Upon hearing the tragic news, Thomas and Watkins were said to be devastated.
"We had all grown up together and were as close as a family," her bandmates said in a statement released Friday. "Today we have truly lost our sister."
TLC was recently in the studio as late as last November recording tracks for their upcoming album, which was due to be released this summer.
"Lisa had a tremendous spirit and loved making music. Her unique talents will be a great loss to the music industry," said Bill Diggins, President of Diggit Entertainment on behalf of TLC. "We all loved Lisa very much. Our hearts go out to her family, and our prayers are with them at this tragic time."
Lopes' death comes less than a year after another popular female R&B star, Aaliyah, died tragically in a plane crash in the Bahamas last August.
Born in Philadelphia on May 27, 1971, Lopes formed TLC with Thomas and Watkins in 1992. Following the release of their debut album, Oooooooh...On the TLC Tip, the Atlanta-based trio achieved megastardom with their multiplatinum-selling album CrazySexyCool, which spawned the hit ballad "Waterfalls" as well as an accompanying multimillion-dollar video that won four MTV Video Music Awards.
CrazySexyCool also snagged TLC Grammys for best R&B Album and R&B performance for the song "Creep." Backed by her bandmates soulful singing, Lopes added fast-paced, high-pitched rhymes to the group's unique sound, helping them win over critics who initially tagged them gimmicky for wearing condom-laced clothing as a fashion statement.
But as TLC's fame grew, so did Lopes' reputation for being the "crazy" one in the group--as opposed to Thomas, who was the "sexy" one, and Watkins, who was the "cool" one.
In 1994, Lopes pleaded guilty to arson after burning down the million-dollar mansion of her boyfriend, former Atlanta Falcons football star Andre Rison one night after the couple had an argument. She was sentenced to a stay in a halfway house, five years probation, and fined $10,000.
While the pair split, Rison eventually forgave her and the couple got back together, only to break up again. The twosome soon reconnected again and announced plans to tie the knot In July, 2001. But the date came and went without a wedding. (At last check, both Rison and Lopes had still been an item.)
Constant feuding between "Left Eye" and her bandmates often fueled talk that TLC was breaking up, rumors that Watkins firmly denied last year.
"With three women, you agree to disagree. I'm not always going to agree with Lisa and she's not always going to agree with me, that's fine," she told the Associated Press in an interview last year.
The group proved its staying power with the success of its last album, Fanmail. Released in 1999, the record sold more than eight million copies, and a year later, TLC members took a break to work on various solo projects.
In late 2000, Lopes pulled a bizarre move and vanished without a trace after missing a major press conference. Concern later died down amid reports she had been spotted with then-boyfriend Sean Newman in London (supposedly shopping for wedding rings), as well as in New Orleans, Chicago and Honduras.
That year also saw Lopes embark on a solo project titled Supernova, which was supposed to come out stateside last August, but ended up being permanently shelved by Arista.
She later split from the label as a result of a contractual breach on Arista's part, gave herself a new nickname, N.I.N.A. ("New Identity Not Applicable") and signed with rap mogul Marion "Suge" Knight's newly renamed Tha Row Records (formerly Death Row) intending to release another solo effort.
No word on whether Arista plans to release Supernova in the wake of Lopes' death. There's also no word yet on funeral services.
(Updated at 10:45 a.m. PT)