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We present a case of a forty-eight-year-old woman who discovered by chance that she had macrocytic anemia and thrombocytopenia. Her serum folate and vitamin B12 levels were normal. However, pernicious anemia was suspected due to the presence of indirect signs of a cobalamin deficiency, such as elevated levels of homocysteine and methylmalonic acid, and signs of dyserythropoiesis on the bone marrow aspirate. Checks done on vitamin B12 levels found normal but fluctuating results. Anti-intrinsic factor antibodies were present at a very high level, which explained the fluctuations and the interference found on the assay using competitive binding chemiluminescence (CBLA). Serum vitamin B12 testing by electrochemiluminescence, a method designed not to interfere with intrinsic factor antibodies, showed a collapsed vitamin B12 level. The measurement of vitamin B12 with CBLA, after adsorption of immunoglobulins in the sample using protein G Sepharose™, confirmed the interference of the cobalamin assay with autoantibodies. This case illustrates the difficulties regarding the analysis and standardization of the vitamin B12 assay for the diagnosis of pernicious anemia.