Vazquez, who leaves just days after making the show's final 12, will be replaced by Nikko Smith, who was cut from the competition last week.
"Mario Vazquez has withdrawn from the competition for personal reasons," the network said in a statement. "Smith was chosen to return because he received more votes than Travis Tucker during last week's competition."
FOX had no further comment. Vazquez tells TV Guide he quit "to take care of some personal issues with my family in New York. And with Idol being a live show, it just wouldn't have worked out schedule-wise. I'm healthy, I'm fine. It's just a personal family thing. My family is my top priority."
"Look at me, I'm fine, I'm still kicking," his mother, Ada, said. "I don't know his reasons, but whatever they are, I respect him for it and will be very supportive."
Vazquez, who performed songs such as the Bee Gees' "How Can You Mend a Broken Heart," Stevie Wonder's "Do I Do" and the O'Jays' "I Love Music," became a frontrunner with both fans and fellow finalists: Contestants Carrie Underwood and Anthony Federov both picked him as their favorite so far in the competition.
Meanwhile, the remaining men (Fedorov, Bo Bice, Constantine Maroulis, Anwar Robinson, Scott Savol and Smith) and women (Underwood, Lindsey Cardinale, Mikalah Gordon, Jessica Sierra, Vonzell Solomon and Nadia Turner) will return to the Idol stage Tuesday at 8 p.m., followed by the elimination episode on Wednesday.