The painting is currently in the Stadel Museum in Frankfurt. For a long time, the attribution of this piece was in question, but a restoration job in the 1990s cleared all doubt. It reexposed the painting on canvas, which experts agreed was an autograph. The painting features St. Mark leaning on an open window that frames the upper part of his body. He is in red garb and a gold-yellow hat. To his left and sitting on the window, is a large volume book with a red cover.

A gold-coloured fruit that looks like an apple with a single leaf is on the window sill as well. St. Mark appears to be in the middle of a conversation with his right hand resting on his bearded cheek. Just above St. Mark's head is a plant hanging from the sides of the window. The green and red of the leaves and fruits blend effortlessly with the rest of the scene. Mantegna gave the subject depth, so it seems like St. Mark is leaning out of the window. Given the mystery around the creation of the painting, it is unclear what the context was for this particular subject.

It is speculated that Mantegna did this piece when he was around 17 years of age. He was a young painter in Padua, a region known for breeding internationally acclaimed artists. St Mark the Evangelist shows inspiration from the contemporary art production of that era. The Italian artist is keen on detail in this painting from the expression on St. Mark's face to the straps on the leather-bound volume. The artwork displays a prominent sense of realism that brings the subject to life like St. Mark's raised eyebrows.

Influences from Netherlandish art are apparent in the surface texture. Key contributors from that region, of which there were many, included Jan van Eyck, Rogier van der Weyden, Hieronymus Bosch and Pieter Bruegel. The painting was analysed using infrared reflectography and x-ray photography, which revealed that the piece underwent significant revisions during execution.

St. Mark the Evangelist is one of the first pieces that Andrea Mantegna did, and it provides a few insights of where the artist started. It shows a great understanding of classic architectural motifs using a simple window. St Mark the Evangelist (1448) is a further testament of what Mantegna was able to achieve even at an early age.