Three remarkable new species of Acalypha (Euphorbiaceae, Acalyphoideae) from Madagascar are described and illustrated. Acalypha isaloensis, found in the Isalo Massif of southwestern Ihorombe region, is morphologically similar to A. gracilipes, but differs by its habit, indument, presence of domatia, and inflorescence sexuality. This is the first report of pocket-shaped domatia in the genus. Acalypha rabesahalana and A. tremula, found in Diana and Sava regions in the far north of Madagascar, superficially resemble A. menavody, but they do not strongly resemble any other species known from Madagascar nor from mainland Africa. Preliminary conservation assessments of the three new species are provided, and all are considered endangered or critically endangered, despite occurring in legally protected areas.