Pfeiffera is a genus of epiphytic, terrestrial and epilithic cacti. Its acceptance, circumscription and closest relatives have been debated. In the context of a phylogenetic survey of epiphytic cacti, we have studied relationships in Pfeiffera, sampling eight of nine species and using sequence data from three group II introns (trnK, rpl16, trnG), four intergenic spacers (psbA-trnH, trnQ-rpsl6, rps3-rpl16, trnS-trnG) and the rapidly evolving gene matK of the plastid genome. Phylogenetic analyses revealed Pfeiffera to be polyphyletic, comprising two unrelated lineages, both highly supported. One clade includes the type species, P. ianthothele; the second contains two Pfeiffera and an erstwhile Lepismium species. Our results justify generic status for this newly found clade. Since it includes the type species of the earlier-proposed monotypic genus Lymanbensonia, we suggest the reinstatement of the latter in an amplified circumscription. The necessary new combinations for Pfeiffera brevispina and Lepismium incachacanum are provided. Our results further support the establishment of a separate tribe Lymanbensonieae, formally proposed here, to contain Lymanbensonia and Calymmanthium. The phylogenetic results imply that epiphytism evolved more frequently in Cactaceae than hitherto assumed and further show that morphological convergences in the family can be extreme. An integrated approach using morphology and sequence data is therefore needed to establish sound generic limits in the Cactaceae.