We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35-64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value < 0.0001). No difference was observed for perceived mental health (P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values < 0.05). Treatment targeting specific lymphedema-related symptoms in addition to size/volume reduction may improve some aspects of HRQoL among affected women.