Lewis was last seen at approximately 3:45 a.m. on May 18, 2005, when she left her home on Princeton Avenue southwest in Birmingham, Alabama to go to her job at Children's Hospital. She had been employed as a cook at the facility for seven years. She was not scheduled to start work until 5:00 a.m., but she often went there early.

While on the way to work, Lewis called her brother and said she had a flat tire, and asked him to come help her. He went to the location she specified, but neither Lewis nor her vehicle was there. She never arrived at the hospital and has never been heard from again. Lewis's brother stated that his sister's tires were brand new and he did not believe they had really gone flat. Her blue 2001 Chevrolet S10 pickup truck with the Alabama license plate number YOBOS was found abandoned on May 22 at a gas station on Bankhead Highway in Midfield, Alabama. There was no sign of her at the scene, but witnesses reported seeing a man driving the truck after her disappearance.

Penny L. Clark, a resident of Bessemer, Alabama, is considered a person of interest in Lewis's case because her fingerprints were found on Lewis's truck. Authorities are not referring to her as a suspect, but they would like to locate and question her. John Dubose is another person of interest. He was jailed on unrelated charges after Lewis vanished, then released from custody in 2010. His whereabouts after that are unknown.

Foul play is suspected in Lewis's case. Her disappearance remains unsolved.