According to ABC affiliate WLS-TV in Chicago, officials said the woman's co-worker shook out a sock that had been dropped off as a donation around 9:45 a.m. Friday in the backroom of the thrift store in the 9400-block of South Ashland Avenue.
A gun fell out, police said, and discharged when it hit the floor.
A 54-year-old woman was fatally struck by a bullet in the chest.
The victim has not been identified.
WLS-TV and Sun-Times Media, LLC contributed to this report.