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Synadenos was a close friend to his cousin, the junior emperor Michael IX Palaiologos, but after Michael's death in 1320, Michael's father, the old emperor Andronikos II (r. 1282–1328), distrusting his loyalty, sent him to the border with Serbia, as governor of Prilep.
The Byzantinist Donald Nicol, who researched the family's history, categorically identifies him as the brother of George Palaiologos Kantakouzenos; Giovanni Musachi makes him the brother of Irene Kantakouzene, wife of Serbian Despot Đurađ Branković, but incorrectly states Thomas was the son of the Emperor John VI Kantakouzenos, an error DuCange repeats.