Andrea Meldola was born in Zadar in which members of his family, natives of Romagne, for many generations behave military service in the army of Venetian Republics. In an unknown time he leaved town of birth and went to Venice where he stayed until his death which was documented by his will opened in the year 1563. Situation on Apennine peninsula in the times of Cinquecento, was complex on many levels. In addition to religious turbulence and many conflicts between Italian cities-states, in accordance with the birth of the new superpowers in the west, and expanding of the Ottoman Empire in the east, at that time in the artistic plan enigmatic Mannerist style was dominating which was for centuries underestimated by art historians and theorists. Reviewing the theoretical basis of the origin and nature of that style, which after the Sack of Rome in 1527 began to spread in northern Italy, and its manifestations in the Venetian painting, otherwise tightly related to the Renaissance tradition, we can conclude that it was Meldola who played a very important role in forming variant of the Venetian maniera. It also seems that the end of his life was affected by religious events like problems which the Council of Trent (1545-1563) tried to solve for almost twenty years, which was visible in his last works. Starting his creativity by unseen using of technique with visible brush strokes that shocked contemporaries, it seems that finally he calmed down from the initial severity and audacity, and in the end soothed his own temperament towards proto-Baroque religiosity. However, the key importance of Meldola's role in the context of its time and style lies not in the formation of the Venetian Mannerism, nor in proto-Baroque tendencies, which were very present in his last works, but right in experiments, courage and technical innovations that separate him from his contemporaries.