OBJECTIVE: To determine the neural substrates of biased spatial orienting in posterior cortical atrophy (PCA) by using a combined structural and functional neuroimaging approach. BACKGROUND: Patients with spatial neglect typically bisect horizontal long lines towards their brain lesions but the precise neural substrates of this spatial bias remain controversial and poorly explored in neurodegenerative disorders such as PCA. METHODS: 15 patients with PCA underwent brain MRI and single photon emission computed tomography (SPECT) and were required to bisect five 20 cm long lines, each centred on an A4 horizontal sheet. Direct correlations between average deviations on the bisection task and both (1) the degree of grey matter density, as estimated by voxel based morphometry and (2) regional cerebral blood flow, as assessed by SPECT, were performed. RESULTS: Seven patients (47%) had pathological bias on the bisection task, deviating consistently towards the non-neglected side for each of the five lines. Rightward bias (sign of left-sided neglect) was more frequent and severe than leftward bias (sign of right-sided neglect). Correlation analyses showed that rightward deviations correlated with atrophy and hypoperfusion exclusively in the right hemisphere, involving a large scale fronto-parietal network; cortical atrophy was prominent in the parieto-temporal cortex but extended to the frontal region; hypoperfusion was substantial both in the middle frontal gyrus and in the postcentral region. No correlations emerged from leftward deviations. CONCLUSION: The results indicate that rightward bias (sign of left-sided neglect) in PCA depends on dysfunction of a large fronto-parietal network in the right hemisphere, related to both cortical atrophy and decreased cerebral perfusion.