From the victory of the third season of the reality show Grande Fratello (Big Brother, 2000 to present), which jettisoned him to fame and led him to be cast by Ferzan Ozpetek in Saturno contro (Saturn in Opposition, 2007), to the protagonist role in films such as Il grande sogno (The Big Dearm, 2009) and Diverso da chi? (Different from Whom?, 2009), and to an important cameo in an international blockbuster such as Eat Pray Love (2010), the career of Luca Argentero found its crowning achievement in the titular role of Doc Nelle tue mani (Doc—In Your Hands, 2020 to present), a series which is now considered abroad as a most representative Italian medical drama. This study of Argentero focuses more specifically on his peculiar cross-media and cross-genre trajectory: it will open with a brief discussion of his participation in one of the earliest and most iconic editions of Grande Fratello, to switch to an overview of his film roles, paying particular attention to those early performances that came to define the “training” stage of his career. In particular, the chapter looks at his approach to romantic lead roles through characters that cover a wide spectrum of sexual orientations.