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. In the South Side section of the city, PA 378 intersects with the northern terminus of PA 412 (Broadway). 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 travels through Bethlehem, transforming from a two-lane residential street into Wyandotte Street. It then connects with the northern end of PA 412 (Broadway) in the South Side area. The route continues northward and provides access to PA 412 via a ramp leading to 3rd Street, widening to four lanes at that point.