BACKGROUND: Invasive electroencephalogram (EEG) studies are often considered necessary to localize the epileptogenic zone in partial epilepsies associated with focal dysplastic lesions (FDL). Our aim was to evaluate the relationships between subtraction ictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) hyperperfusion clusters and MRI-visible FDL, and to establish a preliminary algorithm for a noninvasive presurgical evaluation protocol for MRI-visible FDLs in patients with refractory epilepsy. METHODS: Fifteen consecutive patients with refractory partial epilepsy and a single MRI-visible FDL underwent a noninvasive presurgical evaluation including SISCOM. Each hyperperfusion cluster was visually analyzed, automatically quantitated, and its distance form the lesion as outlined on the MRI was measured. In patients who underwent surgery, the volumes of resected brain tissue containing the FDL, the SISCOM hyperperfusion cluster, and surrounding regions were assessed on postoperative MRI and correlated with surgical outcome. RESULTS: Fourteen of the 15 patients (93%) showed SISCOM hyperperfusion overlapping with the FDL. The FDL was detected only after reevaluation of the MRI guided by the ictal SPECT in 7 of the 15 patients (47%). Four distinct hyperperfusion patterns were observed, representing different degrees of seizure propagation. Nine patients have been operated on. Five have been seizure-free since surgery and one since a reoperation. The degree of resection of the MRI-visible FDL was the major determinant of surgical outcome. Full resection of the SISCOM hyperperfusion cluster was not required to render a patient seizure-free. CONCLUSION: Detailed analysis of SISCOM hyperperfusion patterns is a promising tool to detect subtle FDL on MRI and to establish the epileptic nature of these lesions noninvasively. Overlap between the SISCOM hyperperfusion cluster and MRI-visible FDL in a noninvasive presurgical evaluation with concordant data may suffice to proceed to epilepsy surgery aimed at removing the MRI-visible FDL and the part of the hyperperfusion cluster within and immediately surrounding the FDL.