Within Rubiaceae, one of the most taxonomically problematic assemblages is the Psychotria–Palicourea complex, largely due to its high species richness, unstable generic boundaries, and marked morphological variability. The genus Mexocarpus was originally established to accommodate Palicourea tetragona, distinguished by its pyrenes bearing prominent ridges—an unusual trait compared to other members of Palicourea. This taxon occurs from southern Mexico to Central America and, apart from its distinctive pyrenes, is characterised by elongated white flowers with nocturnal anthesis and fruits that become tetragonal when dry. The species was first described under Cephaelis, later transferred to Palicourea, and subsequently placed in Mexocarpus. However, this last reassignment has been contested by some authors, who argue that pyrene morphology is too variable to justify generic separation. To clarify the phylogenetic position of Mexocarpus tetragonus, we performed phylogenetic analyses using two nuclear DNA markers (ETS and ITS) and one plastid marker (trnL–F) under Maximum Likelihood and Bayesian inference. The resulting molecular phylogeny indicates that M. tetragonus lacks phylogenetic support for generic distinction, forming an unresolved clade with P. tomentosa and P. faxlucens. Furthermore, comparative morphological assessments with closely related taxa demonstrate that pyrene characters are highly variable and show overlapping variation, rendering them unsuitable as diagnostic features for defining a separate genus. Based on combined molecular and morphological evidence, we therefore recommend treating Mexocarpus as a synonym of Palicourea.