It occupies roughly the two sides of the early stretch of Via Tiburtina, starting from Termini railway station and ending at the Verano area.

Originally a working-class neighbourhood (its inhabitants were mostly workers of the Wuehrer Brewery and the freight yard), it has been a popular, left-oriented area.

During World War II San Lorenzo was heavily bombed by Allied planes (on 1943-07-19); the only massive bombing of Rome during the war (though not the only air raid on the city), it aimed at disrupting the railway communication pivoting on the nearby huge freight yard; however, it caused also extensive damage to the buildings of the district (including the Policlinico Umberto I and the basilica itself) and killing some 1,500 people.

Maria Montessori's first school (for pupils ages 3-6) was started in San Lorenzo in 1907 under the name "La casa dei bambini".

[1] Today San Lorenzo, due to the vicinity of the La Sapienza University, is increasingly assuming the character of a student and young artist district.