- Jan 21 Juan de Grijalva, Spanish conquistador (c. 1489)
- May 6 Karel van Bourbon, military governor (Lombardije), dies at 37
Niccolo Machiavelli
Jun 21 Niccolo Machiavelli, Florentine statesman and author, dies at 57
- Jul 28 Rodrigo de Bastidas, Spanish conquistador (founded city of Santa Marta), murdered by some of his men
- Aug 3 Scaramuccia Trivulzio, Italian cardinal
- Nov 8 Jerome Emser, German theologian (b. 1477)
- Nov 15 Princess Catherine of York, 9th child and sixth daughter of King Edward IV by his wife Elizabeth Woodville, dies at 48
- Nov 20 Wendelmoet "Weyntjen" Claesdochter, 1st Dutch woman burned as heretic