The purpose of the study was to assess whether non-enhancing adjacent cortical signal intensity abnormality detected on fluid-attenuated inversion recovery (FLAIR) can differentiate between multicentric and/or multifocal glioma and non-glioma pathology in patients with multiple enhancing cerebral lesions. Nineteen MR studies were reviewed after a database search and exclusion criteria applied, to detect areas of FLAIR cortex involvement without enhancement. Statistical analysis was carried out using a 2 x 2 contingency table and Fischer's exact ratio. Non-enhancing adjacent cortical T2 signal abnormality was seen in eight of eight multicentric and/or multifocal gliomas and four of 11 of the non-glioma pathologies (10 metastatic disease and 1 lymphoma). The presence of non-enhancing adjacent cortical T2 signal abnormality had a sensitivity of 100% and specificity of 63% for glioma. The positive predictive value was 67% and negative predictive value 100%. Fischer's exact probability test was P = 0.01 when applied to the glioma versus non-glioma categories, indicating a significant difference. Non-enhancing adjacent cortical T2-weighted FLAIR signal appears to be more frequently seen in patients with glioma and multiple enhancing lesions compared with those with glioma and a solitary enhancing cerebral lesion. The absence of this sign favours metastatic disease and the presence suggests that multicentric and/or multifocal glioma should remain a consideration.