Here are few stories of times that somebody other than the wife of the president has served as First Lady.
Jefferson
Martha Wayles Jefferson, the wife of third president Thomas Jefferson, died at age 33 in 1782—nearly 20 years before Jefferson took office in 1801. So, stepping in to take on the First Lady’s duties of the time as White House hostess was Jefferson and Wayles’s 28-year-old daughter, Martha Jefferson Randolph. At the time, “Patsy” Jefferson was married to Thomas M. Randolph, Jr., who would go to be elected governor of Jefferson’s home state of Virginia.
Jackson
President Andrew Jackson’s wife, Rachel Donelson Jackson, died in December 1828 at age 61—just six weeks after the election, but before the Inauguration. The couple had no biological children, but adopted several over the years, including a nephew who they renamed Andrew Jackson, Jr., a Creek boy orphaned in the War of 1812, and a grandson of Donelson’s sister. But the First Lady had to be a woman, so stepping in was Donelson’s 21-year-old niece, Emily, who as a child had lived with the Jacksons for a while.
Jackson, 2nd Term
Donelson’s duties ended in 1834, during Jackson’s second term. Presidential cabinet member John Eaton (Secretary of War) married a woman named Peggy O’Neale, a relationship widely gossiped about in Washington as it had likely begun as an affair while both were previously married. Many wives of cabinet members gave the Eatons the cold shoulder, including acting First Lady Emily Donelson. President Jackson thought this mean and unacceptable, and in 1834 he took on a new substitute First Lady, his daughter-in-law, Sarah Yorke Jackson.
Cleveland
Grover Cleveland is the only president to serve two non-consecutive terms, and he’s also the only president to get married while Commander-in-Chief. In 1886, a little over a year into his first term, Cleveland married Frances Clara Folsom, who took on the duties of First Lady. But before the marriage took place, Cleveland’s younger sister, Rose Cleveland, was the acting First Lady.