The purpose of this study was to correlate serum vitamin D levels with potential clinical variables and to determine the extent of vitamin D deficiency in a large, outpatient oncology practice. One hundred ninety-five consecutive patients referred for consultation at a community radiation oncology center from October 8, 2008 to March 17, 2010 had vitamin D levels ordered. Patients who were deficient in vitamin D were treated with replacement therapy. Demographic and medical data were collected prospectively and subsequently analyzed. Pretreatment baseline patient and tumor characteristics were evaluated with respect to vitamin D concentrations. One hundred and sixty patients were analyzed. A total of 74% of patients had 25-hydroxyvitamin D concentrations considered either deficient (<20 ng/mL) or suboptimal (20-30 ng/mL). Replacement therapy raised serum vitamin D levels by an average of 15 ng/mL (95% CI = 11-18, P < 0.01). Lower than median serum vitamin D levels were associated with stage III disease in univariate analysis [OR = 2.6 (95% CI = 1.1-6.2), p = 0.04] as well as multivariate analysis adjusted for age, sex, body mass index, and season of draw [OR = 3.3 (95% CI = 1.1-9.7), P = 0.03]. Three-quarters of patients in our series had suboptimal or deficient circulating concentrations of 25-hydroxyvitamin D. Low serum vitamin D levels, independent of age, sex, and body mass index, predicted advanced stage disease.