The lousy disease (phthiriasis) and its potentially deadly consequences is well attested from antiquity until the 19th century. Intensely itching, vesicular or tumorous skin lesions defile the body and release swarms of insects spontaneously or after incision. Several well-known persons from antiquity and the early modern period are supposed to have died of the lousy disease. Both classicists and physicians have questioned the credibility of said accounts. By means of our interdisciplinary approach based on an analysis of different descriptions of the lousy disease from antiquity to the 19th century, this paper will present strong arguments for the existence of a potentially lethal form of phthiriasis. In contrast to its name, the lousy disease was most likely caused by a species of mites, similar to the one causing cystic subepidermal tumors in birds.