The station was designed to replace Porta Tosa station (opened in 1846 as the terminus of the line to Treviglio and eventually Venice) and Porta Nuova station (opened in 1850 as the second terminus on the line to Monza, which was eventually extended to Chiasso) and was interconnected with all lines, either existing or under construction, surrounding Milan.
The main destinations are Calalzo, Venezia, Trieste, Udine, Vicenza, Portogruaro and Milano.
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Immediately after the crash, the nearby Milan central railway station, metro station and the Linate airport were shut down.
The main destinations of passengers embarking at the station are Ventimiglia, Genoa and Milano Centrale.
The most important destinations are Monselice, Rovigo, Verona Porta Nuova, Modena, Milano Centrale, Codogno and Cremona.