The origins of the territory - which, as for the landscape, social and cultural aspect is now totally similar to Appio-Latino - can be dated back to the Middle Age, when the road that gave it its name, the Via Tuscolana, was first mentioned in a papal seal Honorius III issued in 1217.

The road was built to link Rome with Tusculum but does not seem to have a classical origin: nothing to do with the road has the imperial mausoleum known as Monte del Grano (which was related to the nearby Roman villa called Ad Duas Lauros), nor do the columbaria of Via Pescara, which were probably built along a cross street of the Via Labicana.

Up to the 1930s, the territory was also cut through by the Acqua Mariana, which is dated back to 1122 by the Liber Pontificalis: it was commissioned by Pope Callixtus II to allow the irrigation of the Ager Lateranense, the fields surrounding Saint John Lateran.

To the south-west, it borders with Quartiere Appio Claudio (Q. XXV): the boundary is delineated by the stretch of Via del Quadraro between Via Tuscolana and Via Appia Nuova.

To the south, the quarter borders with Quartiere Appio-Pignatelli (Q. XXVI), from which it is separated by the stretch of Via Appia Nuova between Via del Quadraro and Via dell'Almone.