Line S5, a cross-city route, heads initially in a southerly direction from Varese to Gallarate, and then southeasterly to Rho.

On 1 July 2008, responsibility for operating the line passed to a joint venture comprising Trenitalia, FNM and ATM.

[5] The joint venturers had won a tender that had been launched by the region in 2004, and had pledged to provide free transport of bicycles on public holidays.

[7] In May 2011, as a result of the merger between the regional passenger division of Trenitalia and the FNM subsidiary LeNORD, the merged entity, Trenord, took over the two railway companies' roles in the joint venture.

The stations on the S5 are as follows (stations with blue background are in the municipality of Milan):[8] S5 trains are made up of a 3-car Treno Servizio Regionale (TSR) combined with a 5-car TSR, except on Saturdays and Sundays, when 3-car TSRs are used on some trains, and 5-car TSRs operate the remaining, more heavily patronised services.