|Covid-19|January 14 – The classical statue of Laocoön and His Sons is unearthed in Rome. On the recommendation of Giuliano da Sangallo and Michelangelo, Pope Julius II purchases it and places it on public display in the Vatican a month later.
January 22 – The Swiss Guard arrives at the Vatican, to serve as permanent ceremonial and palace guards under Pope Julius II.
April 18 – Pope Julius II lays the foundation stone of the new (current) St. Peter's Basilica in Rome, replacing the Old St. Peter's Basilica.
August 6 – The Grand Duchy of Lithuania defeats the Tatars of the Crimean Khanate in the Battle of Kletsk.
August 19 – Sigismund I the Old succeeds his brother as king of Poland.
November 6 – Pope Julius II personally leads his troops into Bologna, retaking the city from the excommunicated tyrant Giovanni II Bentivoglio.
The Portuguese mariner Tristão da Cunha sights the islands of Tristan da Cunha, naming them after himself.
In Ming dynasty China, the costs of the courier system are met by a tax in silver on land instead of corvée labor service.
Duarte Barbosa returns to Lisbon.
Johannes Trithemius becomes abbot of the monastery of St. Jacob at Würzburg.
Leonardo da Vinci completes most of his work on the Mona Lisa.
February – George Buchanan, Scottish humanist scholar (d. 1582)
February 2 – René de Birague, French cardinal and chancellor (d. 1583)
February 15 – Juliana of Stolberg, German countess (d. 1580)
March 3 – Luís of Portugal, Duke of Beja (d. 1555)
April 7 – Francis Xavier, Spanish Jesuit saint (d. 1552)
April 13 – Peter Faber, French Jesuit theologian (d. 1546)
July 1 – Louis II of Hungary and Bohemia (d. 1526)
August 12 – Franciscus Sonnius, Dutch counter-Reformation theologian (d. 1576)
October – Louis de Blois, Flemish mystical writer (d. 1566)
December 4 – Thomas Darcy, 1st Baron Darcy of Chiche, English courtier (d. 1558)
December 8 – Veit Dietrich, German theologian, writer and reformer (d. 1549)
Vicente Masip, Spanish painter (d. 1579)
William Paget, 1st Baron Paget, English statesman (d. 1563)
Ii Naomori, Japanese samurai (d. 1560)
Elizabeth Barton, English nun (d. 1534)
Margaret Lee, confidante of Queen Anne Boleyn (d. 1543)
May 4 – Sultan Husayn Mirza Bayqara, Timurid ruler of Herat (b. 1438)
May 20 – Christopher Columbus, Italian explorer (b. 1451)
August 15 – Alexander Agricola, Flemish composer (b. c. 1445)
August 19 – King Alexander Jagiellon of Poland (b. 1461)
September 13 – Andrea Mantegna, Italian painter and engraver (b. 1432)
September 25 – King Philip I of Castile (b. 1478)
undated - Mihri Hatun, Ottoman poet
Year 1506 (MDVI) was a common year starting on Thursday (link will display the full calendar) of the Julian calendar.