The theft occurred Thursday as the bills were being transported from Dallas to New Jersey, CNNMoney reported.
"We're following all logical leads," said FBI spokesman Frank Burton Jr.
Burton declined to comment on the amount taken, but said it was substantial.
The bills have a design that will not be in circulation until 2013. The back features a large gold "100" graphic and the front features an orange area containing a faint image of the Liberty Bell.
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