Duffy's Cut is the name given to a stretch of railroad tracks about 30 miles (48 km) west of Philadelphia, Pennsylvania, originally built for the Philadelphia and Columbia Railroad in the summer and fall of 1832. The line later became part of the Pennsylvania Railroad's Main Line. Railroad contractor Philip Duffy hired 57 Irish immigrants to lay this line through the area's densely wooded hills and ravines. The workers came to Philadelphia from the Ulster counties of Donegal, Tyrone, and Derry/Londonderry to work in Pennsylvania's nascent railroad industry. While their fates are unclear, a theory based on a record from a railroad archive suggests all 57 died of cholera during the second cholera pandemic. The remains of seven have been discovered at the site, and forensic evidence suggests that some may have been murdered, perhaps due to fear of contagion as the pandemic spanned several continents over many years. While this has become the most popular theory, a coroner who studied the bones believes the alleged bullet holes and injuries were actually due to natural decomposition and post-mortem damage.

Philadelphia and Columbia Railroad (P&CR) (1834) was one of the earliest commercial railroads in the United States, running 82 miles (132 km) from Philadelphia to Columbia, Pennsylvania, it was built by the Pennsylvania Canal Commission in lieu of a canal from Columbia to Philadelphia; in 1857 it became part of the Pennsylvania Railroad. It is currently owned and operated by Amtrak as its electrified Keystone Corridor. The Philadelphia and Columbia Railroad's western terminus was located near the former ferry site known as Wright's Ferry, in the town once of that name, but now Columbia in Lancaster County. There the P&CR met with the Pennsylvania Canal—navigations and improvements on the Susquehanna River east bank approximately 30 miles (48.3 km) south of Harrisburg, Pennsylvania. Most of its right-of-way was obtained by the actions of the Pennsylvania Canal Commission which operated the railroad under the various enabling acts of the Pennsylvania legislature known as the Main Line of Public Works in support of a far sighted plan to link the whole state by canals. With an engineering study reporting back a finding that obtaining sufficient waters to flood the intended 80+ mile canal from Philadelphia to Columbia, the Canal Commission and legislature authorized the railway on the right of way intended for the canal.