We present a patient with positive medium titer MOG-IgG and progressive neurological decline whose clinical and radiological phenotype were not consistent with a MOG-IgG associated disorder and ultimately received a diagnosis of glioblastoma after brain biopsy and died 4 weeks later. This represents an important topic with a high frequency of MOG-IgG testing in clinical practice. Due to this there are increasing reports of MOG-IgG positivity in atypical clinical phenotypes, raising the possibility of false positives, which can have important implications. It is important to highlight that judicious clinical evaluation is needed when interpreting MOG-IgG results in atypical settings.