Thieves struck at the Western Union outlet on main street in Highgate, St. Mary late Wednesday night into Thursday morning, removing the vault.
It is not yet known if money was inside.
The thieves entered the building by cutting the padlock to the grille and removing the glass panes on the door.
In June, a vault containing more than $7 million was stolen from the Western Union outlet in Oracabessa, St. Mary.