U.S. Route 222 Business is a 12.17-mile (19.59 km) business route of US 222 in Reading, Pennsylvania. The southern terminus is at US 222 in Cumru Township. Its northern terminus is at US 222 in Ontelaunee Township. The route begins at the US 222 freeway and heads through the southwestern suburbs of Reading as Lancaster Avenue, intersecting Pennsylvania Route 724 in Shillington. US 222 Bus. continues into Reading on Lancaster Avenue and intersects the northern termini of PA 625 and PA 10 before reaching an interchange with the US 422 freeway.

U.S. Route 222 is a U.S. Highway that is a spur of US 22 in the states of Maryland and Pennsylvania. It runs for 95 miles (153 km) from US 1 in Conowingo, Maryland, north to the junction of Interstate 78 (I-78) and Pennsylvania Route 309 in Dorneyville, Pennsylvania. US 222 is almost entirely in Pennsylvania, and serves as the state's principal artery between the Lancaster and Reading areas in the west and the Lehigh Valley in the east.