OBJECTIVE To assess changes in social and neuro-cognition and regional cerebral blood flow (rCBF) in schizophrenic patients with psychotic syndrome treated with Social Skill Training (SST). METHODS 17 patients underwent two high resolution rCBF SPECT at rest before and after a one-year treatment with SST. Patients were assessed using a neuropsychological evaluation (W.A.I.S.-R, T.M.T, Verbal Fluency, W.C.S.T.). SPM8 was used to investigate rCBF changes from the pre- to the post-SST condition and the relationship between rCBF and clinical scores used as covariates of interest. RESULTS All patients presented with an improvement in social perception, ability to deal with abstract social conventions, rules and judgments about people (Comprehension and Picture Completion sub-tests) and some neuro-cognitive functions sustaining the process of socially relevant information. The main effect of SST was to produce rCBF increases in precuneus, PCC, superior parietal lobules, PMC, pre-SMA, precentral gyrus, dmPFC, dlPFC, vmPFC, OFC (p<0.0001 uncorrected). The SPM analysis showed that Comprehension was supported by PMC, dmPFC, OFC and vmPFC, while the Picture Completion was supported by PMC and dmPFC (p&lt;0.0001). CONCLUSIONS SST in schizophrenic patients improves resting neural activity in cortical areas of the amigdala-based and non-amygdala networks of social brain, including dmPFC and vmPFC, and dlPFC, which are known to be part of default mode and task-positive networks and to be implicated in schizophrenia.