This study explores the relationship between body mass and femoral construction in armoured (dasypodids and manids) and unarmoured (caviomorph rodents) mammals. Predictive equations based on diaphyseal cross-sectional parameters provided the most accurate estimates of body mass in caviomorph rodents and dasypodids. When these equations are applied to the estimation of body mass in manids, relatively low predictive errors (<20%) are found only when caviomorph equations derived with diaphyseal cross-sectional area or moments of area are used. Dasypodid equations generally yield less accurate estimates for manids, so that armouring of the integument alone poorly discriminates femoral types. Other factors with potential to differentially impact femoral construction are also considered: although locomotor speed strongly influences mass–structure relationships within caviomorph rodents, the confounding influence of locomotor posture, fossoriality, and arboreality render these relationships less predictable across all three groups considered here. Limb structure and, hence, scaling patterns of each phylogenetic group are influenced by a unique mosaic of factors that is difficult to summarize quantitatively. The results of the study provide cautions as well as encouragements for the estimation of body mass for fossil species that have no adaptively similar living relatives.