Background: Breast cancer-related lymphedema (BCRL) is a long-term health problem often causes pain, disability and interferes with the activities of daily living. Multi-waved Locked System (MLS) laser and Cold Compression therapy (CCT) showed favourable results in many trials. Yet, no comparisons were conducted to compare their effects. Purpose: To compare the effect of MLS laser versus CCT on lymphatic flow, volumetric measurements and health-related quality of life (HRQL) in BCRL patients. Subjects: Sixty-six female patients, with mean age 37.4 ± 5.39 years, mean weight 74.5 ± 7.31, mean height 1.637± 0.057 and Body mass index 27.8 ± 1.79 were diagnosed with BCRL participated in this study. Methods: Patients were randomly divided into 3 groups; MLS group: 22 patients received MLS laser and the conventional treatment. CCT group: 22 patients received CCT and the conventional treatment. Control group: 22 patients received the conventional treatment only. Interventions were performed for 20 sessions (5 sessions/ week) over a period of four weeks. Outcomes were assessed at the beginning and at the end of treatment using lymphoscintigraphy, volumetric measurements and Lymphedema Life Impact Scale (LLIS). Results: The studied groups were comparable regarding demographics with small size effect in between the groups. Also, there was no statistically significant difference between the 3 groups regarding lymphatic flow, limb volume and LLIS score with small size effect. After treatment, there were variable degrees of improvement and statistically significant differences with large size effect regarding lymphatic flow, limb volume and LLIS score. Conclusion: Study results support that CCT is an effective new modality in the treatment and rehabilitation of BCRL, it resulted in greater improvements and is superior to the MLS laser.