ABSTRACT About 25-50% of women who undergo breast cancer surgery develop persistent chest wall pain and shoulder mobility limitations following surgery. The pain and mobility limitations adversely affect quality of life, sleep, and body image. Unfortunately, current treatments for pain and mobility limitations have variable efficacy. Based on a review of relevant pre-, intra-, and post- operative factors, we reasoned that myofascial massage may address contributors to pain and mobility limitations following breast cancer surgery. Myofascial massage is a deep tissue massage that focuses on muscles as well as the connective tissue that surrounds muscles, bones, and ligaments. We subsequently conducted a pilot randomized controlled trial involving 21 women with persistent pain and mobility limitations many months after surgery. We found that women who received myofascial massage to the affected breast/chest/shoulder had marked reductions in pain and mobility limitations and significant improvements in quality of life compared to a control group who received relaxation massage. We also established a practice- based research network of 63 northeast Ohio massage therapists to guide future work. We now propose a full scale randomized controlled trial involving 202 women with persistent pain and mobility limitations. To help differentiate between the specific effects of myofascial massage and non-specific effects due to prolonged touch and attention from a massage therapist, we will include an active control group that will receive light touch. Participants in each group will receive 30 minutes of treatment twice weekly for 2 months. Primary analyses will determine the impact of myofascial massage on pain and mobility limitations. Secondary analyses will examine the impact of myofascial massage on a number of secondary outcomes, including range of motion, quality of life, sleep, and body image. Innovative features of the proposed project include a rigorous randomized controlled trial design, inclusion of an active control group, direct targeting of the affected breast/chest/shoulder, assessment of multiple mechanistic and patient-centered outcomes, and involvement of a massage practice-based research network. We anticipate that the project will lead to a new and effective approach for addressing a major source of morbidity for women with breast cancer. Furthermore, the project may serve as a model for future trials of manual therapy among individuals with chronic medical conditions.