This large portrait is almost two metres tall and came a few years before El Greco moved from Italy to Spain. He was still working in the style of the great Italian masters at this point, having concentrated on Italian art during his formative years. He was strongly religious and also included this type of content within many of his paintings, both in scenes from the Bible, but also with portraits of members of the church, as found in front of us here. Whilst this portrait of Charles de Guise may not be amongst his most famous paintings of all, it offers us an important addition to his work in the early 1570s, just before a significant change in his artistic style was about to take place. The cardinal sits side-on, staring off to our left hand side, where as most later portraits by El Greco would normally have the subject face the viewer directly. He had his right hand on a book, no doubt serving a symbolic role, and his left hand hangs from an arm rest. The bright red tones of his garment are suited to the bright palette often chosen by El Greco.

We can spot perhaps a reflection from a mirror or window to the left hand side in the background which will remind many of the Dutch Golden age, and perhaps in Flemish art even before that. There are other additions in the background but within a darkened setting which makes them hard to see clearly. The main focus therefore is on the subject directly in front of us and the artist allows light to reflect across the surface of his clothing, helping us to determine the materials used, as well as bringing the whole painting to life. El Greco produced portraits throughout his career and truly mastered this genre, which was a necessary means to generating income during the 16th and 17th century. Prior to photography and other modern formats, portraiture was a popular way of ensuring one's legacy, placing a great importance on the best artists, such as El Greco. He would produce portraits of several cardinals in both Italy and Spain.

There was an evolution of El Greco's style through the course of his life, and the work he completed in Spain tends to be received with the most enthusiasm today. However, these works from before his move to Spain are also highly important, and also technically impressive. He could have been assumed to be Italian himself in the manner that he worked at that point, and it is worth remembering that his home region of Crete was actually under the rule of Venice in the early years of his life. Few painters would be able to achieve success in two major European nations as El Greco would do, and he embraced both cultures to the full, fusing elements of both together in his evolved artistic style. He remains one of the most popular European painters from this era.