Abstract Objective The objectives of this study were to determine whether patients reporting symptoms are more likely to develop lymphedema and to describe the temporal relationship between symptom onset and lymphedema. Methods This was a prospective longitudinal cohort study of 647 women treated for breast cancer and screened for lymphedema using arm volume measurements and subjective questionnaires (n = 647; 2284 questionnaires [median 3.5 per patient, range = 1–24]). Primary study outcome was lymphedema (relative volume change ≥10%). The Kaplan–Meier method was used to estimate cumulative lymphedema incidence. Cox proportional hazards models were used to assess the relationship between symptoms, other risk factors, and lymphedema. Results A total of 64 patients (9.9%) developed lymphedema. On multivariable analysis, patients reporting increased arm size (hazard ratio = 3.09, 95% CI = 1.62–5.89) were more likely to progress to lymphedema than those who did not report this symptom. Of those who developed lymphedema, 37 (58%) reported an increased arm size a median of 6.1 months before lymphedema onset (range = 68.6 months before to 50.2 months after lymphedema onset). Conclusion Patients at risk of lymphedema who report increased arm size might do so prior to lymphedema onset and are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without objective or observable edema, these patients should be followed vigilantly and considered for early intervention. Symptoms should be incorporated into screening and diagnostic criteria for lymphedema. Impact This study shows that patients at risk for breast cancer–related lymphedema who report increased arm size should be considered at high risk for progression to lymphedema—even without edema on measurement or clinical examination—and should be followed vigilantly, with consideration of early intervention. Lay summary If you are at risk of lymphedema and you feel as though your arm size has increased, you might develop lymphedema, and you are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without measurable or observable edema, you should be followed vigilantly and consider early intervention.