This chapter pursues several goals. First, it considers face as a multivalent universal permanent sign that serves as a bridge between nature and culture, multilayerd biosemiosis and cultural semiosis at the intersection between various traditions and civilizations. Second, it unravels the story of the centuries-old decoding of the face-sign in the light of the now-forgotten Aristotelian semiotic theory and its postulates. Third, it brings to the surface of cultural history, philosophy and semiotics little-known analytical contribution by Dr. Paolo Mantegazza (1831–1910), whom I label as the "Italian Freud", whose theory of metoposcopy covers the pathway from Aristotle, the renaissance up to modernity via such thinkers as Spontoni, Darwin, Bell and others.This study does not limit its thematic orientation to the face-sign but it posits Mantegazza's work as a transition from the ancient facial semiosis to the broader issue of eudomonism in cultural history. In contrast to Darwin and Freud, Mantegazza's approach is culture predicated rather than biology-defined. With the help of the face-sign and the theory of metoposcopy, Mantegazza articulates much more—he raises the universe of facial semiosis to the level of and an instrument of evaluating culture and human values. Mantegazza elevates reason, artistic creativity and all that makes homo sapiens stand above in the natural universe and be happy in it, deriving pleasure and happiness from becoming civilized.