PURPOSE: To analyze the topography of the epileptogenic zone (EZ) and the etiologic substrate as risk factors for sleep-related focal epilepsy. METHODS: Three hundred three patients (172 males and 131 females, mean age at surgery 25.6 +/- 13.1 years), who were seizure-free after resective surgery for drug-resistant focal epilepsy, were retrospectively reviewed. Statistical analysis was conducted to evaluate the risk of presenting sleep-related epilepsy (SRE) against topography of resection (assumed to correspond or to include the EZ) and results of histology. RESULTS: Thirty-nine patients (12.8\%) presented with an SRE. At bivariate analysis, a higher frequency of SRE was associated with a frontal lobe EZ (p = 1.94 x 10(-9)) and Taylor's FCD (TFCD, p = 2.20 x 10(-16)), whereas architectural FCD (p = 0.00977), ganglioglioma (p = 0.02508), and mesial temporal sclerosis (p = 2.47 x 10(-5)) were correlated with a reduced frequency of SRE. Multivariate analysis demonstrated that the only variable significantly associated with SRE was the presence of a TFCD, which increased 14-fold the risk of SRE [p = 1.66 x 10(-10); risk ratio (RR) = 14.44]. DISCUSSION: In this study, we have demonstrated a significant and strong association between SRE and TFCD in a select population of patients with drug-resistant focal epilepsy submitted to surgical resection of the EZ. Although our results cannot be applied to the entire spectrum of SRE, the presence of TFCD as the underlying etiology should be considered when evaluating patients with SRE, because surgery can provide excellent results on seizures in these cases.