The highway connects the Tramway community with Sanford's Jonesboro Heights neighborhood.

NC 78 is a 4.6-mile (7.4 km) two-lane highway, traversing from US 1/US 15/US 501 in Tramway, to US 421 Business/NC 42/NC 87 in Jonesboro Heights.

[3] By the late 1960s, NC 78 was rerouted again to its current terminus with Horner Boulevard.

In 1940, it was renumbered as NC 381, which was synched with SC 381 in South Carolina.

[citation needed] The entire route is in Lee County.