Background: Research has shown that women with large and hypertrophic breast sizes report an increased prevalence and severity of musculoskeletal pain in the upper torso. Despite this evidence, factors contributing to the development of musculoskeletal pain among these women are poorly understood, and the threshold at which breast size becomes problematic in terms of musculoskeletal pain is currently unknown. Methods: Three hundred Australian women (aged 18 to 82 years) who volunteered as participants were divided into four breast size groups (small, breast volume <350 ml; medium, breast volume 350 to 700 ml; large, breast volume 701 to 1200 ml; and hypertrophic, breast volume >1200 ml). The thoracic flexion torque, thoracic kyphosis angle, total upper torso musculoskeletal pain score, and regional upper torso musculoskeletal pain scores derived for participants in the four groups were compared using an analysis of covariance design, controlling for age and body mass index. Results: Thoracic flexion torque significantly increased as breast size group increased. Women with hypertrophic breasts reported significantly higher total upper torso musculoskeletal pain scores compared with women who had small, medium, and large breasts, and this was significant for the upper back, shoulders, neck, and breasts. No significant difference was found in thoracic kyphosis angle among the four groups. Conclusions: Musculoskeletal pain became most pronounced in women with hypertrophic breasts who had the greatest breast volume and displayed the greatest thoracic flexion torque. Clinical and/or surgical treatment for symptomatic relief should aim to either counteract thoracic flexion torque or reduce breast volume.