There is inconclusive evidence on the role of dietary intake of vitamin B12 in cancer. We evaluated the association between vitamin B12 intake and cancer risk in a hospital-based case-control study, comprising 3,758 cancer cases and 2,995 controls in Vietnam. Vitamin B12 intake was derived from the validated food frequency questionnaire. Unconditional logistic regression model was used to calculate the odds ratios (ORs), and respective 95% confidence intervals (CIs) for the association between vitamin B12 and cancer risk. There was a U-shaped association between vitamin B12 intake and overall risk of cancer. Individuals with intakes lower than the median intake had a 6% (OR = 1.06, 95% CI: 0.86-1.31)-107% (OR = 2.07, 95% CI: 1.58-2.71), increased risk of cancer (Ptrend<0.001), whereas those with higher intakes than the median intake had a 20% (OR = 1.20, 95% CI: 0.97-1.48)-52% (OR = 1.52, 95% CI: 1.22-1.89) increased risk of cancer (Ptrend<0.04). The excess risk of cancer associated with low intakes of vitamin B12 was observed among esophageal, lung, and breast cancer patients, whereas with high intakes of vitamin B12 among gastric cancer patients. In summary, a U-shaped association between vitamin B12 intake and increased cancer risk was observed in the Vietnamese population.