Focal cortical dysplasia type IIB (FCDIIB) is a developmental malformation of the cerebral cortex that is associated with pharmacoresistant epilepsy. Overexpression of adenosine kinase (ADK) has been regarded as a pathologic hallmark of epilepsy. We hypothesized that the epileptogenic mechanisms underlying FCDIIB are related to abnormal ADK expression. We used immunohistochemistry to examine the expression of ADK and of heterogeneous cell population markers of astrocytes (glial fibrillary acidic protein), immature glia (vimentin), immature neurons (neuronal class III beta-tubulin, TUJ1), multipotential progenitor cells (nestin), mature neurons (microtubule-associated protein 2), and antiapoptotic gene products (Bcl-2) in surgically resected human epileptic cortical specimens from FCDIIB patients (n = 20). Expression patterns were compared with those in normal autopsy (n = 6) and surgical control (n = 6) brain samples. Balloon cells in FCDII lesions were immunoreactive for ADK (77%) and balloon cells expressing the different cell markers expressing different degrees of ADK. Adenosine kinase expression assessed by Western blot and enzymatic activity were also greater in FCD versus control samples. These results suggest that upregulation of ADK is a common pathologic component of FCDIIB. Adenosine kinase might, therefore, be a target in the treatment of epilepsy associated with FCD.