ImportanceRecent recognition of the overdiagnosis and overtreatment of ductal carcinoma in situ (DCIS) detected by mammography has led to the development of clinical trials randomizing women with non–high-grade DCIS to active surveillance, defined as imaging surveillance with or without endocrine therapy, vs standard surgical care.ObjectiveTo determine the factors associated with underestimation of invasive cancer in patients with a clinical diagnosis of non–high-grade DCIS that would preclude active surveillance.Design, Setting, and ParticipantsA retrospective cohort study was conducted using records from the National Cancer Database from January 1, 1998, to December 31, 2012, of female patients 40 to 99 years of age with a clinical diagnosis of non–high-grade DCIS who underwent definitive surgical treatment. Data analysis was conducted from November 1, 2015, to February 4, 2017.ExposuresPatients with an upgraded diagnosis of invasive carcinoma vs those with a diagnosis of DCIS based on final surgical pathologic findings.Main Outcomes and MeasuresThe proportions of cases with an upgraded diagnosis of invasive carcinoma from final surgical pathologic findings were compared by tumor, host, and system characteristics.ResultsOf 37 544 women (mean [SD] age, 59.3 [12.4] years) presenting with a clinical diagnosis of non–high-grade DCIS, 8320 (22.2%) had invasive carcinoma based on final pathologic findings. Invasive carcinomas were more likely to be smaller (>0.5 to ≤1.0 cm vs ≤0.5 cm: odds ratio [OR], 0.73; 95% CI, 0.67-0.79; >1.0 to ≤2.0 cm vs ≤0.5 cm: OR, 0.42; 95% CI, 0.39-0.46; >2.0 to ≤5.0 cm vs ≤0.5 cm: OR, 0.19; 95% CI, 0.17-0.22; and >5.0 cm vs ≤0.5 cm: OR, 0.11; 95% CI, 0.08-0.15) and lower grade (intermediate vs low: OR, 0.75; 95% CI, 0.69-0.80). Multivariate logistic regression analysis demonstrated that younger age (60-79 vs 40-49 years: OR, 0.84; 95% CI, 0.77-0.92; and ≥80 vs 40 to 49 years: OR, 0.76; 95% CI, 0.64-0.91), negative estrogen receptor status (positive vs negative: OR, 0.39; 95% CI, 0.34-0.43), treatment at an academic facility (academic vs community: OR, 2.08; 95% CI, 1.82-2.38), and higher annual income (>$63 000 vs <$38 000: OR, 1.14; 95% CI, 1.02-1.28) were significantly associated with an upgraded diagnosis of invasive carcinoma based on final pathologic findings.Conclusions and RelevanceWhen selecting patients for active surveillance of DCIS, factors other than tumor biology associated with invasive carcinoma based on final pathologic findings may need to be considered. At the time of randomization to active surveillance, a significant proportion of patients with non–high-grade DCIS will harbor invasive carcinoma.