The late early Miocene Santa Cruz Formation of southern Argentina is one of the most productive fossil mammal-bearing formations in South America. Hundreds of species have been named from this formation, resulting in a clear overestimation of Santa Cruz mammal diversity. Recent paleoecological studies have attempted to minimize this problem by analyzing more restricted faunal lists based only on recently collected fossil samples. In some cases, this approach has excluded clearly recognizable Santa Cruz taxa. In this study, I use a family-level rarefaction analysis of the Yale Peabody Collection of Santa Cruz fossils to test whether such absences are likely due to smaller sample size or to other factors. I further attempt to reconcile these absences using distributional data from recent and historical Santa Cruz Formation collections. The rarefaction analysis indicates that most single-locality samples from the Santa Cruz Formation have lower familial diversity than expected based on the taxonomic distribution of specimens in the Princeton University Collection at Yale Peabody Museum (YPM-PU) as a whole. However, I conclude that single-locality samples are not necessarily more appropriate than multi-locality samples for paleoecological analyses of ancient Santa Cruz Formation mammal communities given the large regional extent of the Santa Cruz Formation and the large geographic area encompassed by most modern communities used for comparison. This study highlights the need for more precise stratigraphic correlations among Santa Cruz localities and integration of important historical collections into a modern stratigraphic framework.