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OBJECTIVE We evaluated prospectively the association between incident early- (diagnosed before 40 years of age) and later-onset type 2 diabetes and early- (diagnosed before 50 years of age) and later-onset cancer risk. RESEARCH DESIGN AND METHODS We prospectively followed 228,073 eligible participants in the Nurses' Health Studies for up to 38 years. Hazard ratios (HRs) and 95% CI were estimated using Cox models. RESULTS We documented 18,290 type 2 diabetes, 6,520 early-onset cancer, and 36,907 later-onset cancer cases during follow-up. In fully adjusted analyses, early-onset type 2 diabetes was associated with increased risk of early-onset total cancer (HR [95% CI] 1.47 [1.06-2.04]), diabetes-related cancer (2.11 [1.38-3.23]), and obesity-related cancer (1.75 [1.08-2.82]), and the risk elevations were restricted to those with a BMI at 18 years of age of ≥21 kg/m2 (total cancer: 1.75 [1.20-2.56]; diabetes-related cancer: 2.43 [1.50-3.94]; and obesity-related cancer: 1.84 [1.05-3.22]). Early-onset type 2 diabetes was associated with higher risk of later-onset diabetes-related and obesity-related cancer specifically among individuals with higher BMI at 18 years of age. Later-onset type 2 diabetes was associated with a higher risk of later-onset total cancer (1.15 [1.11-1.20]), diabetes-related cancer (1.17 [1.12-1.22]), and obesity-related cancer (1.18 [1.13-1.24]). In analyses based on refined timing, the HRs attenuated substantially with aging. CONCLUSIONS Incident early-onset type 2 diabetes was associated with increased risk of early-onset total cancer and diabetes- and obesity-related cancer, especially in those with higher BMI at 18 years of age. The impact of early-onset type 2 diabetes on cancer risk may be inherently stronger than that of later-onset type 2 diabetes. ARTICLE HIGHLIGHTS The relationship between incident early- and later-onset type 2 diabetes and risk of early- and later-onset cancer is unclear. We investigated this topic based on 228,073 U.S. women and up to 38 years of follow-up. Our findings suggested that incident early-onset type 2 diabetes was associated with increased risk of early-onset total cancer, and diabetes- and obesity-related cancer, especially in those with higher BMI at age 18 years. Cancer prevention efforts tailored for patients with early-onset type 2 diabetes may need to focus on those with higher adolescent or emerging adulthood BMI. The impact of early-onset type 2 diabetes on cancer risk may be inherently stronger than that of later-onset type 2 diabetes.