Ecological studies have long described a higher incidence of ovarian cancer in more extreme latitudes, where sun exposure, and presumably vitamin D exposure, is lower. Basic science studies have also noted polymorphisms of the vitamin D receptor in ovarian cancers. The aim of this study is to examine the relationship of serum vitamin D to ovarian cancer.A case-control study of 7273 subjects from the National Health and Nutrition Examination Surveys (NHANES) was performed. Serum 25-hydroxyvitamin D (25[OH]D) levels were examined in both ovarian cancer patients and a control population. Logistic regression examined the odds of ovarian cancer for those with vitamin D levels below the median of the U.S. population.Ovarian cancer cases were more than three times more likely to have low 25[OH]D levels (OR 3.68, 95% CI 1.03-13.21, p=0.04). In the weighted multivariate model, the relationship persisted after adjusting for potential confounders, including age, body mass index, and diet. Adjusting for significant covariates, which included age and dietary calcium intake, ovarian cancer cases were nearly four times more likely to have low 25[OH]D levels (OR 3.92, 95% CI 1.11-13.85, p=0.03).Prevalent ovarian cancer cases have lower serum 25-hydroxyvitamin D (25[OH]D) than the general population. Deficiency in vitamin D may provide an etiologic link between the long-known ecologic findings regarding latitude and the basic science noting polymorphisms in the vitamin D receptor.