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January 18 - King Christian II of Denmark and Norway defeats the Swedes at Lake Asunde.

June - Moctezuma II, Aztec ruler of Tenochtitlan is declared deposed due to his captivity by conquistador Hernán Cortés. His brother Cuitláhuac rises to the throne.

June 7 - Field of Cloth of Gold. Famous meeting between King Henry VIII of England and King Francis I of France.

July 1 - The forces of Cuitláhuac, Aztec ruler of Tenochtitlan gain a major victory against the forces conquistador Hernán Cortés. This La Noche Triste (Night of Sorrow), results in the death of about 400 conquistadors and some 2,000 of their Native American allies. However Cortés and the most skilled of his men manage to escape and later regroup.

September 22 - Suleiman I succeeds his father Selim I as Sultan of the Ottoman Empire.

October - Cuitláhuac, Aztec ruler of Tenochtitlan dies from smallpox. He is succeeded by his nephew Cuauhtémoc.

November 8 - Stockholm Bloodbath begins: A successful invasion of Sweden by Danish forces under the command of Christian II of Denmark results in the execution of around 100 persons (mostly nobility and clergy involved in the previous Swedish war effort).

November 28 - After navigating through the South American strait, three ships under the command of Portuguese explorer Ferdinand Magellan reach the Pacific Ocean, becoming the first Europeans to sail from the Atlantic Ocean to the Pacific (the strait was later named the Strait of Magellan).

December 10 - Martin Luther burns a copy of The Book of Cannon Law (see Canon Law) and his copy of the Papal bull Exsurge Domine.

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March 3 - Matthias Flacius, Croatian protestant reformer (d. 1575)

August 1 - King Sigismund II Augustus of Poland (died 1572)

August 10 - Madeleine de Valois, queen of James V of Scotland (died 1537)

September 13 - William Cecil, 1st Baron Burghley, English statesman (died 1598)

October 5 - Alessandro Cardinal Farnese, Italian cardinal (d. 1589)

Choi Hyong Ung, Korean monk

Jean Ribault, French navigator (died 1565)

Vincenzo Galilei, Italian music theorist, lutenist, and composer (died 1591)

Aben Humeya, last independent king of Granada (died 1568)

Bess of Hardwick, jailor of Mary I of Scotland (died 1608)

Denis Lambin, French classical scholar (died 1572)

Frans Floris, Flemish painter (died 1570)

Giovanni Battista Moroni, Italian mannerist painter (died 1578)

Hans Eworth, Flemish portrait painter (died 1574)

Ijuin Tadaaki, Japanese nobleman (died 1561)

Jacques Cujas, French legal expert (died 1590)

Johannes Acronius Frisius, German doctor and mathematician (died 1564)

Jorge de Montemayor, Spanish novelist and poet (died 1561)

Leonard Digges, mathematician and surveyor (died 1559)

William Somerset, 3rd Earl of Worcester (died 1589)

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February 5 - Sten Sture the younger, Viceroy of Sweden (born 1493)

April 6 - Raphael, Italian painter and architect (born 1483)

June 24 - Hosokawa Sumimoto, Japanese samurai commander (born 1489)

September 22 - Selim I, Ottoman Sultan (born 1465)

Cacamatzin, king of Texcoco (born 1483)

Cuitláhuac, Aztec ruler of Tenochtitlan

Filippo de Lurano, Italian composer (born 1475)

Jan Lubranski, Polish bishop (born 1456)

Moctezuma II, Aztec ruler (born c1466)

Raphael Urbinas, Italian artist (born 1483)

Sheikh Hamdullah, calligrapher (born 1436)