Few studies have investigated the role of vitamin B12 metabolism in vitiligo. We tested the hypothesis that vitamin B12 and folate metabolism might have an influence on the pathogenesis of vitiligo. Full blood count and levels of folic acid, vitamin B12, homocysteine and holotranscobalamine were examined for 69 patients with vitiligo and 52 controls. The vitiligo group had higher levels of homocysteine (P < 0.01) and haemoglobin (P < 0.01) levels, and lower levels of vitamin B12 (P < 0.01) and holotranscobalamine (P < 0.0001) than the control group. Folic acid levels were similar for both groups. In a risk analysis, hyperhomocysteinaemia (≥ 15 μmol/L, P < 0.01) and vitamin B12 deficiency (< 200 pg/mL, P < 0.01) were significant risk factors for vitiligo. Patients with holotranscobalamine levels in the lowest quartile had an increased risk for co-occurrence of vitiligo (P < 0.005). Vitamin B12 deficiency and hyperhomocysteinaemia may share a common genetic background with vitiligo.