The present study examined cortical oxygenation changes during lexical decision on words and pseudowords using functional Near-Infrared Spectroscopy (fNIRS). Focal hyperoxygenation as an indicator of functional activation was compared over three target areas over the left hemisphere. A 52-channel Hitachi ETG-4000 was used covering the superior frontal gyrus (SFG), the left inferior parietal gyrus (IPG) and the left inferior frontal gyrus (IFG). To allow for anatomical inference a recently developed probabilistic mapping method was used to determine the most likely anatomic locations of the changes in cortical activation [Tsuzuki, D., Jurcak, V., Singh, A.K., Okamoto, M., Watanabe, E., Dan, I., 2007. Virtual spatial registration of stand-alone fNIRS data to MNI space. NeuroImage 43 (4), 1506-1518. Subjects made lexical decisions on 50 low and 50 high frequency words and 100 pseudowords. With respect to the lexicality effect, words elicited a larger focal hyperoxygenation in comparison to pseudowords in two regions identified as the SFG and left IPG. The SFG activation difference was interpreted to reflect decision-related mechanisms according to the Multiple Read-Out Model [Grainger, J., Jacobs, A.M., 1996. Orthographic processing in visual word recognition: A multiple read-out model. Psychological Review 103, 518-565]. The greater oxygenation response to words in the left IPG suggests that this region connects orthographic, phonological and semantic representations. A decrease of deoxygenated hemoglobin was observed to low frequency in comparison to high frequency words in a region identified as IFG. This region's sensitivity to word frequency suggests its involvement in grapheme-phoneme conversion, or its role during the selection of pre-activated semantic candidates.