Assessing skeletal muscle mass (SMM) is critical in studying and detecting sarcopenia. Direct measurements by MRI or computerized tomography are expensive or high in radiation exposure. Dual-energy X-ray absorptiometry (DXA) is promising for body composition assessments, but the validity of DXA for predicting SMM in the elderly is still under investigation. The objective of this study was to assess the relationship between DXA-derived measurements of lean soft tissue mass (LSTM) and SMM in older women. Study participants were postmenopausal women (n = 101) recruited in southern Arizona. Total and regional body composition was measured using MRI and DXA (QDR4500w). The participants' mean age was 70.7 +/- 6.4 y and their mean BMI was 27.4 +/- 5.1 kg/m2. DXA-derived LSTM was highly correlated with MRI-derived SMM for the whole body (r = 0.94; P < 0.001) and leg region (r = 0.91; P < 0.001). In multivariate models, adjusting for age and DXA-derived percent fat slightly increased the amount of variance in SMM that can be explained by the DXA-derived LSTM assessments for the leg region but not for the total body. In conclusion, although the relationships between DXA measures and MRI-derived SMM vary by region of interest, the overall prediction of SMM by DXA is excellent. We conclude that DXA is a reliable method for cross-sectional assessments of SMM in older women.