Conclusive evidence has yet to emerge regarding the association between markers of hyperinsulinemia and breast cancer. We determined the effect of insulin resistance (IR) on breast cancer risk in Latinas of Mexican origin who did not have a direct family history of breast cancer and had not been previously diagnosed with prediabetes or diabetes. This was a case-control study in which a case (n=124) was defined as a patient with a recent histopathologic diagnosis of breast cancer and a control (n=197) was defined as a participant who had recently undergone a mammography and had either a Breast Imaging, Reporting & Data System (BI-RADS)-1 or a BI-RADS-2 score. Plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured. IR was determined by using the homeostasis model assessment (HOMA-IR) criterion. Odds ratios (OR) and 95% confidence intervals (CI) were determined using unconditional binary logistic regression analysis. IR was detected in 33.9% of cases and 41.6% of controls, based on a HOMA-IR ≥3.5. Although multivariate analysis did not show any association between IR and breast cancer risk (OR 0.56, 95% CI 0.31-1.01), it showed that an HbA1c ≥5.7% increased the risk of breast cancer (OR 3.41, 95% CI 1.93-6.01), regardless of menopausal status. The findings suggest that IR had no effect on breast cancer risk; however HbA1c increased the risk in Latinas of Mexican origin who had not been diagnosed previously with prediabetes or diabetes and had no direct family history of breast cancer. Prospective studies are required to establish the impact of IR over time.