The robbery happened around 11:15 a.m. at the Wells Fargo branch at 2005 Market Street.
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According to the FBI and the Philadelphia Police Department's Violent Crimes Task Force, the suspect entered the bank and handed a teller a threatening demand note.
After obtaining an unspecified amount of cash, the suspect fled the area on foot.
The suspect is considered armed and dangerous.
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Anyone with information is asked to call investigators at 215-418-4000.
A reward is being offered for information leading to an arrest, police say, and tipsters can remain anonymous.