Picinisco is a municipality located on a rocky hill at 725 meters above sea level in the Comino Valley, with an area of 6000 hectares, most of which belong to the National Park of Abruzzo, Lazio, and Molise.

The Monte Meta, a mountain range extending from the Sangro to the Volturno, rises with peaks exceeding 2000 meters, and with its sheer sides, divides the landscape into two sectors: one towards the Abruzzo-Molise side and the other towards the Lazio side.

The most important peaks are Monte Petroso (2,249 m), Monte Altare (2,174 m), Monte Tartaro (2,191 m), Torretta di Paradiso (1,976 m), Monte a Mare (2,124 m), Metuccia (2,105 m), Monte Forcellone (2,030 m), Monte Cavallo (2,039 m), and Monte Mare (2,020 m).

The origin of the name Picinisco is not certain, but human presence in the area dates back to ancient times, as evidenced by inscriptions and polygonal wall fragments that attest to the presence of the Sanniti and subsequent conquest by the Romans.

During the Middle Ages, the municipality followed the fate of the nearby cities of Atina and Alvito, of which it was part of the political jurisdiction. The first document mentioning Picinisco dates back to 1017, when the princes of Capua Pandolfo III and Pandolfo IV granted the church of San Valentino, located on the borders of the Comino County, to the Monastery of Montecassino. In 1054, the town was fortified by Oderisio II and Rainaldo III, counts of the Marsi.

The territory of Picinisco became part of the Kingdom of the Two Sicilies in June 1150, when Roger the Norman conquered southern Italy for the crown of Naples. For three centuries, from 1193 to 1503, the territory of Cominense was hit by upheavals, wars and turmoil caused by various foreign dynasties, including Normans, Swabians, Angevins, Aragonese, French and Spanish.

During the succession of dynasties on the throne of Naples, the districts of Cominense were also ceded to different families, and Picinisco passed from the d’Aquino to the Cantelmo, Borgia, Navarro, Cadorna, Matteo di Capua and finally Gallio.

In the sixteenth century, the presence of bandits in Picinisco (from 1590) threatened the peace of the area. Even at the end of the eighteenth century, this phenomenon reoccurred, but with a different character, after the unification of Italy. In 1927, as part of a vast administrative reform of the fascist regime, Picinisco was transferred from the province of Terra di Lavoro to the Lazio Region and became part of the new province of Frosinone.

During World War II, Picinisco was impacted by the consequences of the occupation by German soldiers. The town, located on the Gustav Line, suffered from the rounding up of refugee Jews and the evacuation of the inhabitants. The town was bombed and subjected to harassment. The liberation took place on May 29, 1944, when the town was freed by Italian troops.

After World War II, a serious economic crisis caused a strong emigration, dramatically reducing the population and leaving many hamlets abandoned.

In 1984, Picinisco was hit by a magnitude 5.9 earthquake that damaged the historical center.