1560s, in reference to diseases, "virulent, tending to produce death," from Middle French malignant and directly from Late Latin malignantem (nominative malignans) "acting from malice," present participle of malignare "injure maliciously," from Latin malignus "wicked, bad-natured," from male "badly" (see mal-) + -gnus "born," from gignere "to bear, beget," from PIE root *gene- "give birth, beget."
Earlier in the church malignant "followers of the antichrist," from Latin ecclesiam malignantum in early Church writing, applied by Protestant writers to the Church in Rome (1540s). Of persons, "disposed to inflict suffering or cause distress," from 1590s. As an adjective, Middle English used simple malign (early 14c.), also malignous "poisonous, noxious." Related: Malignantly.