114 Background: We evaluated baseline differences in arm tissue composition (fat mass, lean mass, bone mineral content [BMC] and bone mineral density [BMD]) between the affected and unaffected arms in women with breast cancer-related lymphedema (BRCL). We compared changes in arm tissue composition and self-reported lymphedema symptoms after one-year of weight-lifting vs. usual-care. Methods: We utilized data from the PAL trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy x-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. Results: At baseline, the affected arm had more fat (D= 89.7±21.0g; P < 0.001) and lean mass (D= 149.1±25.3g; P < 0.001), but less BMC (D= -3.2±0.9g; P < 0.001) than the unaffected arm. No difference was observed in BMD. After 12-months of weight-lifting, composition of the affected arm was improved: lean mass (71.2±27.9g; P = 0.01) and BMD (0.01±0.01g; P = 0.02) increased, arm fat percentage decreased (0.01±0.01; P = 0.003). No changes observed in fat mass and BMC. Baseline body mass index and BCRL grade modified the relationship between weight-lifting and tissue composition changes. Increases in lean mass were associated with less severe BCRL symptoms. With every one-percent decrease in arm fat percentage, affected limb volume reduced 13.81mL. Conclusions: Among women with BRCL, affected and unaffected arms differ in tissue composition. These differences may be improved with weight-lifting. Changes in arm tissue composition correlate with improved BCRL symptoms. Investigating the combined effects of exercise and weight-loss on arm tissue composition and BCRL symptoms may provide additional insight to the benefits of lifestyle modification on lymphedema biology. Clinical trial information: NCT00194363.