The S50 line connects Biasca with Bellinzona, Lugano, Varese and Malpensa via Mendrisio.

The S50 trains operate at hourly intervals between 4.30 a.m. and 1.00 a.m. and stop at all regional traffic stations. From 6 a.m. to 12 a.m., all trains run through the Ceneri Base Tunnel.

The coaches of the S50 running southwards from Biasca are located at the rear of the composition behind the S10 coaches. The compositions separate in Mendrisio. The S10 continues to Como S. Giovanni, while the S50 runs to Malpensa airport. At Mendrisio, the S50 is coupled to the S10 running northwards from Malpensa airport. Both lines operate as a single train composition up to Biasca.

It is recommended that all passengers check the travel times for the connection they require.