Prior lesion and functional imaging studies have highlighted the importance of the left ventral occipito-temporal (LvOT) cortex for visual word recognition. Within this area, there is a posterior-anterior hierarchy of subregions that are specialized for different stages of orthographic processing. The aim of the present fMRI study was to dissociate the effects of subword orthographic typicality (e.g., cider [high] vs. cynic [low]) from the effect of lexicality (e.g., pollen [word] vs. pillen [pseudoword]). We therefore orthogonally manipulated the orthographic typicality of written words and pseudowords (nonwords and pseudohomophones) in a visual lexical decision task. Consistent with previous studies, we identified greater activation for pseudowords than words (i.e., an effect of lexicality) in posterior LvOT cortex. In addition, we revealed higher activation for atypical than typical strings, irrespective of lexicality, in a left inferior occipital region that is posterior to LvOT cortex. When lexical decisions were made more difficult in the context of pseudohomophone foils, left anterior temporal activation also increased for atypical relative to typical strings. The latter finding agrees with the behavior of patients with progressive anterior temporal lobe degeneration, who have particular difficulty recognizing words with atypical orthography. The most novel outcome of this study is that, within a distributed network of regions supporting orthographic processing, we have identified a left inferior occipital region that is particularly sensitive to the typicality of subword orthographic patterns. © 2010 Massachusetts Institute of Technology.