Propyrotherium saxeum is one the least known members of Pyrotheria, an enigmatic group of extinct, giant, endemic South American ‘ungulates.’ The species was originally described based upon two isolated cheek teeth and two tusk fragments. Later authors assigned additional isolated teeth to this taxon, but the position within the tooth row of all these teeth remained uncertain, preventing an accurate dental characterization and taxonomic distinction from other related species. Here we reexamine the type specimens of P. saxeum and additional materials previously reported as belonging to this species, and analyze several lots of still undescribed specimens, in order to reconstruct the cheek tooth series. Based on comparisons with better known pyrotheres, we conclude that the most probable cheek teeth formula is P2-M3/p2-m3. The cheek teeth gradually increase in size from front to back, and the upper cheek teeth have a gradual increase in loph curvature, as in Pyrotherium. All cheek teeth are bilophodont, but in premolars the anterior loph/id is transversely shorter than the posterior. All have lingual/labial cingulum/id; P3—M3 are subquadratic and three-rooted; p4—m3 are longer than wide, two-rooted, and bear a variably developed vestige of cristid obliqua. Propyrotherium is distinguishable from Griphodon and Baguatherium, but the distinction between these latter two taxa is uncertain with the current evidence. A revised cladistic analysis confirms that Propyrotherium is one of the earliest diverging pyrotheriids, but the resolution of its relationship with Griphodon and Baguatherium requires further evidence.