The Ramalina farinacea (L.) Ach. complex has a world-wide distribution. The thalli are highly variable both morphologically and chemically, with various β-orcinol depsidones being produced as secondary medullary compounds. In the present study a new, rare chemotype containing cyclographin was detected by HPLC analyses. The aposymbiotically grown mycobionts, isolated from the different chemotypes (containing protocetraric, hypoprotocetraric, norstictic/ salazinic/consalazinic, and cyclographin/virensic acids) exhibited a relatively stable chemical profile in culture; the same or closely related secondary metabolites were biosynthesized under variable culture conditions. In one case, exposure of the culture to a particular set of growth parameters repeatedly led to the production of cyclographin as a major compound. The metabolites present in the Ramalina farinacea complex could be classified as an extended chemosyndrome of biochemically and biosynthetically related depsidones. The new chemotype also differs in morphology, exhibiting a long stranded growth form rather than the more tufted thallus typical of the protocetraric acid chemotype. A molecular phylogenetic analysis of Ramalina, including the most common and the rarest chemotype (the protocetraric acid and cyclographin/virensic acid chemotypes, respectively), suggested monophyly of this species, and its placement in a clade of chemically diverse Ramalina species.