[3][4] After that, the highway enters Lower Saucon Township in Northampton County and crosses under I-78 without an interchange.

Past this, PA 378 heads north through Seidersville, where it passes homes and businesses as a four-lane road parallel to Old Philadelphia Pike.

Descending the mountain, PA 378 bends northwestward as a four-lane road known as Wyandotte Street until leaving the University Heights area near Holy Ghost Cemetery.

PA 378 continues into the city of Bethlehem, where it turns northward into residential areas as a two-lane road and is called Wyandotte Street.

The route continues northward and intersects a ramp to 3rd Street that provides access to PA 412, at which point it widens to four lanes.

PA 378 turns westward through Bethlehem, paralleling Union Boulevard and crossing under Fourteenth Avenue.

The route then turns northward, crossing under Eaton Avenue and a Norfolk Southern rail line and passing the Hal Fenicle Memorial Park.

As part of the Interstate Highway System, the Lehigh Valley Thruway was expected to be designated I-78.

[13] On September 23, 2009, the Pennsylvania Department of Transportation announced plans and designs for an upgrade and redesign of PA 378 through Bethlehem at its interchange with West Third Street, although this met public criticism.

The $5.1 million project will also include a widening of PA 412 between Exit 67 on I-78 and Daly Avenue in Bethlehem to two lanes in each direction.

[14] On November 21, 2009, the project was given funding from the American Recovery and Reinvestment Act of 2009 signed by President Barack Obama in 2009.