The medieval castle of Panaghia is situated on the hill of Apityki (or Pityki), at an altitude of 200m from the sea, almost at the centre of Leros. It owes its name to the church of the Mother of God (Theotokos), where is kept the “Holy Palladium of Lerians”, the icon of Panaghia Odigitria, which miraculously arrived on Leros, during the Iconoclasm period. In a chrysobull of Alexios Comnenos, the castle is referred to as Panteli Castle.  It is built on the foundations of an Ancient Acropolis. It was given its current form by the Knights of St. John, who came after its Byzantine occupants.

The church of Panaghia dates back to the 11th century AD, and the gold decorated icon screen dates back to 1745 AD, same as the Episcopal throne and the pulpit. The church of Aghia Triada still stands in the Castle. It contains fragments of 9th century murals of Aghios Nikolaos. In the same area lies a medieval church, recently dedicated to the Unknown Christian Martyr.

The miraculous icon of Panaghia, dressed in silver and bearing the date 728 AD, was probably painted by Evangelist Luke.

Monk Damaskinos of Leros run a school, from 1726 AD until the mid 19th century AD, elevating education in the island.

The Castle of Panteli is the most important medieval castle of Leros. Tradition has it that, during the iconoclast period, in the 9th century AD, a small arc with the icon of Panaghia (Virgin Mary) placed between to candles, was spotted near Leros.