Uterine leiomyomata (UL) are associated with severe reproductive morbidity and are the primary indication for hysterectomy in the United States. A recent prospective cohort study of Black women reported positive associations between intakes of marine-sourced omega-3 fatty acids and UL risk. We examined whether intakes of dietary fat were associated with UL incidence in a 5-year prospective study of premenopausal Black women living in Detroit who underwent serial ultrasound. At baseline (2010-2012) and 20, 40, and 60 months of follow-up, participants underwent transvaginal ultrasound. Among 1,171 UL-free women at baseline, incident UL were detected in 277 women. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of dietary fat and UL incidence. Intakes of total fat and saturated, monounsaturated, polyunsaturated (PUFA), and trans-fat were not appreciably associated with UL incidence. Intake of the marine omega-3 PUFA, docosahexaenoic acid, was associated with 49% higher UL incidence (quartile 4 vs. 1: HR 1.49, 95% CI: 1.04, 2.14; P trend=0.01). Intakes of total marine omega-3 PUFAs were similarly associated with elevated UL incidence (HR 1.35, 95% CI: 0.94, 1.93; P trend=0.03). It remains unclear whether the fatty acids or persistent environmental pollutants drive the association.