Pennsylvania Route 501 is a north–south state highway in south central Pennsylvania that runs for 39 miles (63 km). Its southern terminus is at U.S. Route 222 and Pennsylvania Route 272 north of Lancaster, and its northern terminus is Pennsylvania Route 895 southeast of Pine Grove. Its designations are Lititz Pike, Broad Street (Lititz), Furnace Hills Pike, and College Street (Myerstown).

PA 501 begins as Lititz Pike at a concurrency with U.S. Route 222 south and an intersection with U.S. Route 222 north/ Pennsylvania Route 272 north of Lancaster. In Manheim Township, PA 501 splits off from U.S. Route 222 south while interchanging with U.S. Route 30. In Neffsville, PA 501 has a concurrency with Pennsylvania Route 722. North of Neffsville, PA 501 passes west of Lancaster Airport and has an entrance from PA 501. North of Lancaster Airport, PA 501 enters the boro of Lititz and becomes Broad Street. In downtown Lititz, PA 501 has a small concurrency with Pennsylvania Route 772. North of Lititz, PA 501 is called Furnace Hills Pike. In Brickerville, PA 501 intersects U.S. Route 322. North of US 322 in Elizabeth Township, PA 501 passes over Interstate 76 (Pennsylvania Turnpike).

As PA 501 enters Lebanon County, it is called Furnace Hills Pike. In Schaefferstown, PA 501 has a three route concurrency with Pennsylvania Route 419 and Pennsylvania Route 897. The concurrency is actually a wrong-way concurrency. North of the concurrency, PA 501 is called College Street. In Myerstown, PA 501 intersects U.S. Route 422.

In Berks County, PA 501 is called Lancaster Avenue and passing through the village of Mount Aetna. Paralleling the Little Swatara Creek, PA 501 has many turns in Tulpehocken Township. In Bethel, PA 501 meets the former U.S. Route 22. North of Old 22, PA 501 intersects Interstate 78 and the current U.S. Route 22 at exit 13. North of I-78, PA 501 continues as Lancaster Avenue into Schuylkill County.

PA 501 enters Schuylkill County as Brookside Road and Bethel Road. Southeast of Pine Grove, PA 501 ends at an intersection with Pennsylvania Route 895.

PA 501 was established in 1928, its northern terminus originally at US 422 in Myerstown. Its number is derived from its parent route of PA 1, now known as U.S. 30. By 1946, the terminus had been moved farther north to US 22 in Bethel. Between 1960 and 1966, the route was extended to its current terminus in Pine Grove.

A realignment of PA 501 is planned in Schaefferstown, eliminating the turns the road makes in the community. The project is expected to cost $10.4 million. On September 2, 2010, a court ruling was made overturning a decision that prevented farmland from being taken to construct the road.