Context The impact of Hashimoto thyroiditis (HT) on the risk of thyroid cancer and its accurate detection remains unclear. The presence of a chronic lymphocytic infiltration imparts a logical mechanism potentially altering neoplastic transformation, while also influencing the accuracy of diagnostic evaluation. Methods We performed a prospective, cohort analysis of 9851 consecutive patients with 21,397 nodules ≥1 cm who underwent nodule evaluation between 1995 and 2017. The definition of HT included (i) elevated thyroid peroxidase antibody (TPOAb) level and/or (ii) findings of diffuse heterogeneity on ultrasound, and/or (iii) the finding of diffuse lymphocytic thyroiditis on histopathology. The impact of HT on the distribution of cytology and, ultimately, on malignancy risk was determined. Results A total of 2651 patients (27%) were diagnosed with HT, and 3895 HT nodules and 10,168 non-HT nodules were biopsied. The prevalence of indeterminate and malignant cytology was higher in the HT vs non-HT group (indeterminate: 26.3% vs 21.8%, respectively, P < 0.001; malignant: 10.0% vs 6.4%, respectively, P < 0.001). Ultimately, the risk of any nodule proving malignant was significantly elevated in the setting of HT (relative risk, 1.6; 95% CI, 1.44 to 1.79; P < 0.001), and was maintained when patients with solitary or multiple nodules were analyzed separately (HT vs non-HT: 24.5% vs 16.3% solitary; 22.1% vs 15.4% multinodular; P < 0.01). Conclusion HT increases the risk of thyroid malignancy in any patient presenting for nodule evaluation. Diffuse sonographic heterogeneity and/or TPOAb positivity should be used for risk assessment at time of evaluation.