Species delimitation in foliose macrolichens has long been dominated by chemotaxonomy, resulting in many examples of seemingly morphologically identical species that differ only in the secondary metabolites they produce. This study examines two such species that are widespread in southeastern North America: Parmotrema madagascariaceum (Hue) Hale and Parmotrema xanthinum (Müll. Arg.) Hale. Drawing on data from biogeography, chemistry, morphology, and molecular phylogenetic analyses of nuclear ribosomal internal transcribed spacer sequence data, the two species are treated as conspecific. A taxonomic treatment is presented along with a discussion of previous studies that have examined the delimitation of species that differ only in the presence or absence of compounds that are accessories in addition to a primary set of substances present in both species.