Mespilus and Crataegus are sister genera in Rosaceae tribe Pyreae. Mespilus has been seen to comprise not only the medlar, Mespilus germanica, of western Eurasia but also the Arkansas, U.S.A. endemic, Mespilus canescens. Crataegus, on the other hand, consists of 140–200 species found throughout the northern hemisphere. Diagnoses of these two genera rely on morphological features of leaves, flowers and fruits. However, character states supposed to be diagnostic of Mespilus occur in species of Crataegus. We used two nuclear (ribosomal ITS and LEAFY intron2) and four intergenic chloroplast DNA regions (trnS-trnG, psbA-trnH, trnH-rpl2, and rpl20-rps12) to estimate the phylogeny of Mespilus and Crataegus. Maximum parsimony, maximum likelihood, and Bayesian analyses all corroborate the sister group relationship between Crataegus and Mespilus, and Crataegus brachyacantha sister to the rest of Crataegus. However, incongruence between chloroplast and nuclear data supports the hypothesis of a hybrid origin for Mespilus canescens, with Crataegus brachyacantha or its ancestor as the maternal parent. Accordingly, we (1) restrict Crataegus section Brevispinae to Crataegus brachyacantha (2) distinguish the Arkansas endemic as a nothospecies; (3) describe a new section and a new nothosection within Crataegus to contain the former species of Mespilus and Crataemespilus; and (4) make two new combinations under Crataegus.