Centuries: 15th century - 16th century - 17th century
- April 21 - Battle of Cerignola. Spanish forces under Hernandez Gonzalo de Cordoba defeat the French under the Duc de Nemours, who is killed. Considered to be the first battle in history won by gunpowder small arms.
- May 10 - Christopher Columbus discovers the Cayman Islands and he names them Las Tortugas after the numerous sea turtles there.
- May 13 - Capture of Naples by the Spanish.
- August 8 - King James IV of Scotland marries Margaret Tudor, daughter of King Henry VII of England at Holyrood Abbey, Edinburgh, Scotland.
- September 22 - Francesco Todeschini Piccolomini becomes Pope Pius III succeeding Pope Alexander VI, but dies on October 18.
- December 29 - Battle of the Garigliano - Spanish forces under Cordoba defeat a French-Italian mercenary army under the Marquis of Saluzzo. The French forces withdraw to Gaeta
- Giuliano della Rovere becomes Pope Julius II succeeding Pope Pius III
- Leonardo da Vinci starts work on the Mona Lisa
- Perpendicular style chapel added to Westminster Abbey
- Battle of Ruvo - French-Spanish Wars in Italy
- Vasco da Gama established India's first Portuguese fortress at Cochin
- Mariotto Albertinelli paints his masterpiece, the "Visitation of the Virgin"
- March 10 - Ferdinand I, Holy Roman Emperor
- August 12 - Christian III of Denmark and Norway (1503-1559)
- Sir Thomas Wyatt a poet and Ambassador in the service of Henry VIII
- December 14 - Nostradamus (astrologer)
- Robert Estienne, printer in Paris, was the first to print the Bible divided into standard numbered verses
- Parmigianino, Italian painter and master draftsman (+ 1540)
- February 11 - Elizabeth of York, Queen consort of King Henry VII of England, dies on her 38th birthday.
- Margaret of York sister of Edward IV of England
- August 18 - Pope Alexander VI
- October 18 - Pope Pius III
- Andreas Proles, German Augustinian theologian
- Piero II de Medici (the Unfortunate), Lord of Florence
- Lorenzo the Popolano, Lord of Piombino\n