At this point, DE 100 turns northwest to form a concurrency with DE 48 on four-lane undivided Lancaster Pike, passing through business areas before crossing the East Penn Railroad at-grade. The road continues through residential and commercial areas, crossing Chestnut Run and widening into a divided highway as it comes to an intersection with DE 141. Here, DE 100 splits from DE 48 by turning northeast to join DE 141 on four-lane divided Centre Road. The road runs through industrial areas, curving north past the Barley Mill Road intersection. The roadway curves northeast and passes under the East Penn Railroad before coming to a partial cloverleaf interchange with DE 52 in Greenville. This interchange has no access from DE 100/DE 141 southbound to DE 52 southbound or from DE 52 to DE 100/DE 141 northbound. Past this interchange, the road curves east, with DE 100 splitting from DE 141 at an at-grade intersection by heading north on two-lane undivided Montchanin Road. Montchanin Road heads south from this intersection to provide access to DE 52.