Low appendicular skeletal muscle mass (ASMM) is associated with premature mortality, hyperinsulinemia, frailty, disability, and low bone mineral density. We explored the potential efficacy of slowly progressive weight lifting to attenuate the decline of ASMM among breast cancer survivors by conducting a post hoc analysis of data from the Physical Activity and Lymphedema trial. Between October 2005 and August 2008, we conducted a single-blind, randomized controlled trial of twice weekly slowly progressive weight lifting or standard care among 295 non-metastatic breast cancer survivors. ASMM was quantified using dual-energy X-ray absorptiometry. Changes in ASMM were evaluated from baseline to 12 months between the weight lifting and control groups using repeated measures linear mixed effects regression models. Over 12 months, participants in the weight lifting group experienced attenuated declines in muscle mass compared to the control group, as reflected by relative ASMM (-0.01 ± 0.02 kg/m(2) vs -0.08 ± 0.03 kg/m(2); P = 0.041) and absolute ASMM (-0.02 ± 0.06 kg vs -0.22 ± 0.07 kg; P = 0.038), respectively. Weight lifting did not alter other body composition outcomes including body mass index, total body mass, body fat percentage, and fat mass compared to the control group. Weight lifting significantly increased upper and lower body muscle strength compared to the control group. The intervention was well tolerated with no serious adverse events related to weight lifting. Slowly progressive weight lifting attenuated the decline of ASMM among breast cancer survivors compared to standard care over 12 months. These data are hypothesis generating. Future studies should examine the efficacy of weight lifting to improve distal health outcomes among breast cancer survivors.