Euphorbia section Poinsettia contains approximately 25 species native to the Americas. This taxon is sometimes treated as an independent genus or as a subgenus of Euphorbia, but it is currently placed within the recently recircumscribed subgenus Chamaesyce. Four species of Poinsettia have been previously reported from Bolivia, and a fifth species, Euphorbia mayfieldii, is herein described. This new species is a narrow endemic currently known from three collections made in the department of Santa Cruz, where it occurs on grassy cliff faces in tropical forest at elevations from 645–700 m. Flowering occurs at least from July to September. It is probably an attractive and conspicuous plant by virtue of the white pigmentation of the subcyathial leaves. Euphorbia mayfieldii is distinctive due to the combination of glabrous stems and leaves, in addition to cauline leaves that are opposite to rarely in whorls of three with an unlobed and mostly entire blade. Within section Poinsettia, strictly opposite leaves are otherwise known only from Euphorbia dentata Michx. and relatives. Euphorbia mayfieldii is distinguished from these in being a glabrous perennial herb with nearly entire leaves; the others are pubescent annuals with coarsely dentate or serrate leaves. A dichotomous key is provided to separate the Bolivian members of section Poinsettia.