About 13 major clades can be recognized within the genus Solanum (Solanaceae) based on chloroplast DNA sequence data. One of these is the Cyphomandra clade, which includes about 50 neotropical species. These have traditionally been placed into two or three sections: S. section Pachyphylla (formerly recognized as the genus Cyphomandra), S. section Cyphomandropsis, and S. section Glaucophyllum (monotypic and sometimes placed in S. section Cyphomandropsis). Phylogenetic relationships among 61 accessions of 35 species of the Cyphomandra clade are investigated using sequence data from the nuclear ITS region analyzed by parsimony and Bayesian inference. The Cyphomandra clade forms a monophyletic group, but the ITS data are equivocal as to the monophyly of sections Pachyphylla and Cyphomandropsis. Four well-supported groups of species can be recognized within the Cyphomandra clade; these conform in part to species groups proposed on the basis of morphology. The distribution of self-incompatible and self-compatible breeding systems is mapped onto the ITS cladogram, and patterns of evolution of enlarged anther connectives, osmophores, and volatile composition are discussed in light of hypothesized phylogenetic relationships.