Although rates for invasive cervical cancer have declined over the past twenty years among Alaska Native women, they continue to show high rates of pre-invasive cervical lesions (cervical intraepithelial neoplasia, or CIN). We investigated risk factors for CIN II/III among Alaska Native women in a pilot case-control study. Cases (n = 26) included women with biopsy-proven CIN II/III, while controls (n = 52) had normal cervical epithelium. The strongest risks associated with CIN II/III were HPV infection of any type (Crude Odds Ratio [OR] 8.4, 95% Confidence Interval [CI]: 2.9-29.4), HPV 16 infection (OR 40.8, 95% CI: 9.4-176.4), and a family history of cervical dysplasia (OR 3.9, 95% CI: 1.3-11.3). We also found that use of depot-medroxy progesterone acetate was associated with CIN (OR 3.0, 95% CI: 1.1-8.5). A larger investigation would be necessary to allow adequate evaluation of these, and other, risk factors for CIN among Alaska Native women.