Agios Nicholas Orphanos part of the Vlatadon Monastery is a small hidden church near the eastern walls, of Upper Town. Due to its location between the houses and its beautiful, well-maintained environment, it may be unnoticed by people that pass by, but on the inside, it has some of the most important artistic achievements of Byzantine hagiography. The Byzantine church was built at the beginning of the 14th century and was a catholic monastery, with the possible founder being the Serbian king Miliutin.

The present church, a one-room wooden-roofed building with a vestibule ending in two chapels to the east, preserves exceptional frescoes, which are considered one of the most complete and impressive Byzantine depictions in Thessaloniki. Like the marble iconostasis with the written decoration, they date back to the years of construction of the temple. Agios Nicholas Orphanos (also known as Saint Nicholas of Orphans) is a World Heritage Site and is considered artistically a representative painting of the Pre-Byzantine Renaissance.