"Sometimes things don't work out the way you hope or want them to," a source tells the outlet.
The couple married in 1997 and together have two children, Elliott, 20, and 6-year-old, Helen Grace.
The isn't the first time the couple have hit a bump in their marriage. De Niro filed for divorce in 1999, but the two reconciled and later renewed their vows in 2004.
De Niro and Hightower were last spotted attending the Tony Awards together in June.
De Niro was previously married to Diahnne Abbott from 1976 to 1988. Together they have two children, Drena, 47, and Raphael, 42. The actor went on to have two more children, twin sons, Aaron and Julian in 1995 with his girlfriend at the time, Touki Smith.
CNN has contacted De Niro's representative for comment.
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