Four gunmen fled in a stolen blue Chevy van that was later recovered on Mantua Avenue near 42nd Street, the spokeswoman said.
According to police, the suspects escaped with three money bags containing more than $1 million in tuition receipts from Penn students. About $30,000 of the money was in cash and the rest was non-negotiable checks or money orders, police said.
The suspects, all armed, approached the guard in a hallway as he exited the cashier's office, police said. After taking the money bags, the suspects fled to the waiting van.
A spokesman for Brooks Armored Car Services Inc., in Wilmington, Del., declined comment.
Penn officials could not be reached for comment.
FBI spokeswoman Linda Vizi described the suspects as four men in their 20s. The FBI, she said, is checking into the possibility that yesterday's robbery might be related to a half-dozen other armored car heists - netting nearly $500,000 - in the Philadelphia area during the last four months.
"We don't know at this point whether they're related," Vizi said.
Authorities have said they suspect the earlier armored car holdups were carried out by a six-man gang.
Two suspects have already been arrested in connection with several of the earlier capers.
Anthony McGoue, of Pine Street near 59th in West Philadelphia, and Thaddeus Garfield, of Markoe Street near Woodland Avenue in Southwest Philadelphia, were arrested July 30.
McGoue, 33, is charged with the May 25 robbery of an armored car guard at an automatic teller machine in Holmesburg. Robbers got away with $76,000 as the guard tried to load the machine at the Pathmark supermarket at Frankford Avenue and Pennypack Street.
Garfield was charged in the June 23 holdup at a Super Fresh market at Mermaid Lane and Crittenden Street in Chestnut Hill. During that robbery, three suspects fled with $13,000 following a gun battle with an armored car guard. No one was hurt.