Abstract Ptaeroxylaceae is an Afro-Malagasy family containing three genera, Bottegoa, Cedrelopsis, and Ptaeroxylon. Although the family is morphologically well delimited, it is currently considered part of the subfamily Spathelioideae in a broadly circumscribed orange family (Rutaceae). The Malagasy Cedrelopsis has traditionally been associated with different families of the order Sapindales and its phylogenetic placement in Rutaceae sensu lato has yet to be tested with molecular data. The present molecular phylogenetic study reaffirms the monophyly of Ptaeroxylaceae and its placement in Spathelioideae. Therefore, molecules and morphology support close affinities between Bottegoa, Cedrelopsis, and Ptaeroxylon and also their current generic circumscriptions. We report a case of an evolutionary change from one-seeded to two-seeded carpels within the Harrisonia-Cneorum-Ptaeroxylaceae clade of Spathelioideae. Finally, the sister-group relationship between the African Bottegoa and the Afro-Malagasy Ptaeroxylon-Cedrelopsis clade suggests an African origin of Cedrelopsis.