Phylogenetic placement of Hydrostachys (Hydrostachyaceae) has long been enigmatic, the highly divergent morphology of Hydrostachys having prevented its confident placement in any clade of angiosperms. Phylogenetic placements using DNA sequence data have varied, with most studies suggesting a placement within Cornales. We conducted a large-scale phylogenetic analysis based on nuclear and chloroplast datasets to re-examine the relationships of the genus and assess the data sources and methodological factors that may cause alternative placements. Hydrostachys was consistently recovered as a member of Cornales in all of our analyses based on 338 single-copy nuclear genes and 78 chloroplast genes, but the divergent matK sequences of Hydrostachys available in GenBank led to different phylogenetic placements. These highly divergent DNA sequences may make phylogenetic placement problematic, and other factors may also impact the placement, including taxon sampling, long-branch attraction, incomplete lineage sorting, and potential artifacts (from contaminants, paralogs, or assembly errors) in the datasets.