The aims of the present study were to explore the relation between ictal scalp EEG patterns and ictal hyperperfusion patterns in patients with unilateral hippocampal sclerosis-associated mesial temporal lobe epilepsy (HS-MTLE) by using semiquantitative single-photon emission computed tomography (SPECT) analysis and to assess clinical significance of ictal hyperperfusion patterns. We studied retrospectively 39 consecutive patients with surgically proven HS-MTLE. All had both interictal and ictal SPECTs with the tracer injection during a complex partial seizure (CPS) typical of MTLE semiology. According to initial ictal discharge (IID) frequency on scalp EEG, two lateralizing patterns were identified: (a) a sustained regular 5- to 9-Hz rhythm with a restricted temporal or subtemporal distribution (group 1); and (b) an irregular 2- to 5-Hz rhythm with a widespread distribution (group 2). We performed group analysis by using statistical parametric mapping (SPM) of paired ictal-interictal SPECTs to identify regions of significant ictal hyperperfusion and compared clinical characteristics, tracer-injection time, semiology, pathologic HS grade, and surgical outcome between two groups. Of the 39 patients, 19 patients (10 males, nine right HS) were designated as group 1, and the remaining 20 patients (eight males, seven right HS), group 2. Group 1 showed hyperperfusion mainly confined to the ipsilateral temporal lobe, whereas group 2 showed widespread hyperperfusion in the extratemporal structures such as ipsilateral basal ganglia, brainstem, and bilateral thalamus, in addition to the ipsilateral temporal lobe. No significant difference was found between two groups in clinical characteristics, injection time, pathologic HS grade, and surgical outcome. Among semiologic features, dystonic limb posturing was more frequently observed in group 2 (p = 0.006). Scalp EEG IID frequency in HS-MTLE can be an important determining factor of ictal hyperperfusion patterns. The lack of difference in surgical outcome between two groups implies that different hyperperfusion patterns, according to their IID frequencies, reflect only preferential pathways of ictal propagation rather than intrinsic epileptogenic region.