Cephalocereus, Neobuxbaumia, and Pseudomitrocereus (Cactaceae, Cactoideae, Echinocereeae) are related genera of columnar cacti native to Mexico with current ambiguous circumscription. We applied maximum parsimony and Bayesian inference methods to reconstruct the phylogeny of the Cephalocereus group using molecular data from seven chloroplast regions (petL-psbE, psbA-trnH, rpl16, rpl32-trnLUAG, trnL-F, trnQrps16, andycf1), simple coded indels, and 46 structural characters. The Cephalocereus group was recovered as monophyletic with high support values, whereas Neobuxbaumia appeared as paraphyletic, due to the polyphyly of Cephalocereus and the derived position of Pseudomitrocereus within this group. Topology was mostly congruent among the different phylogenetic methods explored, and three pervasive clades were observed. Two structural characters were confirmed as synapomorphies for the Cephalocereus group: prismatic crystals in the dermal system and a perianth woody cap persistent in the fruit. The derived position of Pseudomitrocereus suggests that new hypotheses must be explored regarding the possible hybrid origin of this taxon. We propose the transfer of all species of Neobuxbaumia, Cephalocereus, and Pseudomitrocereus to a single genus, in which Cephalocereus takes priority over the other names. Based on our results, a new circumscription for Cephalocereus is proposed, including a taxonomic synthesis, two new combinations (Cephalocereus multiareolatus and Cephalocereus sanchezmejoradae), and a key for species.