Just to the north of Egnatia Street, not too far from the Rotunda, is the Church of Hagios Panteleimon, another of the Byzantine churches of Thessaloniki which is difficult to identify, since its present name is a modern one. It is one of the 15 Paleochristian and Byzantine Monuments of Thessaloniki that were included in the UNESCO World Heritage List in 1988.

Historical research identified the church with the Monastery of the Virgin Peribleptos, also known as the Monastery of Kyr Isaac, from the monastic name of its founder who, under the name Iakovos, was Metropolitan of Thessaloniki between 1295 and 1315. This monastery is connected with a number of distinguished intellectuals of Thessaloniki in the 14th century. The monastery retained the name of its founder after 1548, when it was converted into a mosque with the name Ishakiye Camii. 
The identification of the modern church of Hagios Panteleimon with the Monastery of the Virgin Peribleptos was not universally accepted, and some scholars believe that the Monastery of the Peribleptos already existed in the 12th century, and that the church of Hagios Panteleimon was converted into a mosque about 1500 by Ishak Çelebi, the Kadi of Thessaloniki, after whom it was named. The architecture and painted decoration of the church, however, date it to the late 13th - early 14th century and, together with other evidence, appear to support the former view. From an architectural point of view, the church belongs to the complex tetrastyle cross-in-square type, with a narthex and an ambulatory that ends at the east in two chapels. The ambulatory was destroyed at the beginning of the century, but the chapels survive. We know, however, that the outer faces of the ambulatory were articulated by blind arcading and that it had two tribela on the north and south, two domes in the middle of the north and south sides, and two more at the north-west and south-west corners. The centre of the narthex, too, was covered by a dome, while the side bays were vaulted. The eight-sided dome over the nave is supported on columns and capitals taken from earlier buildings. The triple sanctuary ends in an apse with a five-sided exterior, which has a three-light window in the centre. There are also three-light windows in the drums over the arms of the cross. The decorative brickwork is confined to dentilated bands and rosettes. 

Very few of the original wall-paintings survive. In the prothesis is preserved a representation of the Virgin Orans - in an attitude of supplication with Christ at her bosom, in the type of the intercessor praying for the salvation of mankind. The diakonikon has some of the most important saints of the church, such as Saint Peter of Alexandria, Eustathios of Antioch, and Gregory of Nyssa; these are portrayed in an attitude of reverence towards Saint James the Brother of the Lord, who occupies the position of honor in the apse. This composition has been interpreted as honoring both the Church of Jerusalem, of which James the Brother of die Lord was the first bishop, and also St. James himself, who had the same name as the founder of the church, James, the Metropolitan of Thessaloniki. The art of the wall-paintings has been described as transitional, since they combine the monumental style, anti-classical conception, and modeling of 13th century painting with the color harmony and facial types of 14th century works. The rest of the painted decoration of the church belongs to a Turkish repair at the beginning of the 20th century. The phase when the church was converted into a mosque is represented by the base of the minaret and a marble fountain in the grounds of the building.