It happened shortly before 9:30 p.m. at the Extended Stay at 600 Weston Parkway.
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The victim told police the man displayed a weapon, robbed her of money and fled in a vehicle.
No one was hurt.
Police think the robbery may be connected to other crimes, including a robbery earlier Thursday in Morrisville, and an April 26 robbery of a Circle K in Cary near the motel robbery.
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Cary Police are also working with Raleigh Police to investigate possible connections to a trio of robberies on Capital Boulevard in Raleigh on Wednesday night.
READ MORE ABOUT THOSE ROBBERIES HERE
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