Vitamin D is a fundamental mediator of skeletal metabolism. It also has important nonskeletal actions. We hypothesized that vitamin D deficiency may play an important role in skeletal morbidity and clinical outcomes in MM. We studied 148 newly diagnosed MM patients from January 1, 2004 through December 31, 2008 who had a serum 25-hydroxyvitamin D [25(OH)D] obtained within 14 days of diagnosis. Subjects with vitamin D deficiency [25(OH)D level less than 50 nmol/L (20 ng/mL)] had higher mean values of serum C-reactive protein (CRP) (2.40 mg/L vs. 0.84 mg/L, P = 0.02) and creatinine (1.75 mg/dL vs. 1.24 mg/dL, P = 0.03) and lower serum albumin values (3.12 g/dL vs. 3.39 g/dL, P = 0.003) compared to subjects without vitamin D deficiency. The prevalence of vitamin D deficiency increased in parallel with International Staging System (ISS): 16% of subjects in Stage I, 20% in Stage II, and 37% in Stage III (P = 0.03) were vitamin D deficient. No differences were detected between the two groups in terms of skeletal morbidity. Association of vitamin D deficiency with higher serum CRP, serum creatinine and ISS stage at time of diagnosis suggests that vitamin D deficiency may portend poorer outcomes in subjects with MM. Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.