OBJECTIVES: To evaluate vitamin D status in patients with basal cell nevus syndrome (BCNS) who practice photoprotection because of their genetic predisposition to skin cancer and to determine risk factors for deficiency. DESIGN: Retrospective cohort study. SETTING: Academic medical centers. PATIENTS: Forty-one ambulatory patients with BCNS who participated in a 2-year chemoprevention clinical trial. Population-based controls (n = 360) were selected and matched by age, sex, Fitzpatrick skin type, and season/geography. MAIN OUTCOME MEASURES: Levels of 25-hydroxyvitamin D (25[OH]D) and vitamin D deficiency (defined as a 25[OH]D level of =20 ng/mL). RESULTS: Twenty-three patients with BCNS (56%) were vitamin D deficient. Patients with BCNS had mean 25(OH)D levels below those of the general population (-3 ng/mL; P = .02) and were 3 times more likely to be vitamin D deficient (56% vs 18%; P < .001). Levels of 25(OH)D were lower in patients who were overweight (-3.0 ng/mL; P = .04) and who had blood collected in the winter compared with the summer (-7.1 ng/mL; P < .001). Conclusion: Patients with BCNS may be at increased risk for vitamin D deficiency, depending on their adherence to photoprotection practices.