Two monotypic genera of Mimosoideae from southern South America, Mimozyganthus and Piptadeniopsis, have been particularly difficult to classify and there has been disagreement about their relationships to other legume genera. We undertook a phylogenetic study based on molecular data from the chloroplast and nucleus, and synthesized it with new data from morphology, cytology, and palynology, in order to determine where these genera belong in the mimosoid phylogenetic tree. Mimozyganthus, an enigmatic genus whose unique morphology led workers to consider it transitional between the subfamilies Mimosoideae and Caesalpinioideae, is instead nested among the higher mimosoids on the molecular tree. Careful evaluation of the characters that were considered to be caesalpinioid-like reveals that they are not identical and are independently derived. Piptadeniopsis is most closely related to Prosopidastrum, a primarily Argentinian genus with lomentiform fruits. This is in close agreement with most morphological characters, although the pollen is different in the two genera. Piptadeniopsis, Mimozyganthus, and Prosopidastrum form a monophyletic group on all molecular trees, a result consistent with vegetative and fruiting morphology, but not floral characters. Although the relationship of this group to other taxa is unresolved in the individual molecular analyses, a combined analysis of all molecular data for a subset of the taxa reveals that the three taxa are more closely related to the Leucaena group than to Prosopis. We hypothesize that the unique floral characters of Mimozyganthus may have evolved in response to pollinator selection, and a pollination study is needed to test this hypothesis.