Gianfranco Zappettini attends the Academy of Fine Arts in Carrara. In 1962 he entered the studio of the German architect Konrad Wachsmann in Genoa. These influences his painting, orienting it towards a research of a structural type. Zappettini acquires fundamental aptitudes for his future artistic research: formal and expressive precision, the importance of tradition and experimentation. In 1964 he began his collaboration with the Galleria La Polena in Genoa. In 1968 the German painter Winfred Gaul arrived in Genoa, through whom Zappettini began his acquaintance with the German and Dutch artistic circles. In 1971 he was invited to "Concrete Art", a collective exhibition held at the Westfälischer Kunstverein in Münster under the direction of the director, the critic Klaus Honnef.
At the beginning of the 1970s, groups of artists took shape in Italy and Europe who worked on the minimal elements of the language of painting. From this common feeling, the so-called New Painting was formed, from which the Analytical Painting will then be distinguished, more linked to the analysis of the operative means and pictorial processes. Zappettini contributes to it with numerous writings published in Italian and foreign magazines and with "white" paintings.
In March 1974 he returned to the Westfälischer Kunstverein in Münster for "Geplante Malerei", a collective organized by Klaus Honnef and in 1975, among the many exhibitions, he took part in "Analytische Malerei" at the Galerie La Bertesca in Düsseldorf. The artist begins to work on "superimposed canvases". In 1977 he is invited to Ducumenta 6 in Kassel.
From the end of the seventies the painter decided to isolate himself from the international artistic circuits. The exhibition activity does not cease (in 1981 he participates in the exhibition "Pittura inroot", curated by Achille Bonito Oliva at the Artra Studio Gallery in Milan and in 1982 in "Pittura di corta memoria", curated by Viana Conti, at the Palazzo La Permanente from Milan). He lives a phase of spiritual research that will lead him to travel between Europe, the Middle East and Africa and to approach disciplines such as Taoism, Zen Buddhism and above all Sufism. After pictorial works in which conceptual distancing and irony predominate and after trespassing into photography, his works are now inspired by the symbolic world and metaphysics, thanks to the readings of René Guénon. In 1998 the Villa Croce Museum of Contemporary Art in Genoa dedicated an anthological exhibition to him. In the 2000s, Zappettini concentrated on the symbolism of warp and weft and on the color blue, which was later joined by red, yellow and the return of white. In 2003 he established the Zappettini Foundation for contemporary art in Chiavari. In 2011 he took part in the Venice Biennale and in 2022 the personal exhibition The Golden Age was held in London at the Mazzoleni gallery.