Cyrtopodium izaguirreae, a new species from Uruguay is described and compared with morphologically similar taxa. The species was previously mistaken with C. brandonianum, but differs by smaller flowers, proportionally shorter and broader leaves, and geographic distribution restricted to Uruguay. The pinkish lip resembles C. brandonianum and C. pallidum, but the new species is morphologically and geographically more related to C. kleinii. Cyrtopodium kleinii, previously known only from southern Brazil, is recorded for the first time for Uruguay, where it grows sympatrically with C. izaguirreae. Cyrtopodium brandonianum subsp. lageanum, with which the new species was also previously confused, is raised here to species rank, based on the extension of its known geographical distribution and on morphological, ecological and phenological differences from C. brandonianum subsp. brandonianum. A distribution map, images, conservation assessment, comments, list of materials examined and an identification key are also presented for the species addressed in this study.