It is often implicitly assumed that the neural activation patterns revealed by hemodynamic methods, such as functional magnetic resonance imaging (fMRI), and electrophysiological methods, such as magnetoencephalography (MEG) and electroencephalography (EEG), are comparable. In early sensory processing that seems to be the case, but the assumption may not be correct in high-level cognitive tasks. For example, MEG and fMRI literature of single-word reading suggests differences in cortical activation, but direct comparisons are lacking. Here, while the same human participants performed the same reading task, analysis of MEG evoked responses and fMRI blood oxygenation level-dependent (BOLD) signals revealed marked functional and spatial differences in several cortical areas outside the visual cortex. Divergent patterns of activation were observed in the frontal and temporal cortex, in accordance with previous separate MEG and fMRI studies of reading. Furthermore, opposite stimulus effects in the MEG and fMRI measures were detected in the left occipitotemporal cortex: MEG evoked responses were stronger to letter than symbol strings, whereas the fMRI BOLD signal was stronger to symbol than letter strings. The EEG recorded simultaneously during MEG and fMRI did not indicate neurophysiological differences that could explain the observed functional discrepancies between the MEG and fMRI results. Acknowledgment of the complementary nature of hemodynamic and electrophysiological measures, as reported here in a cognitive task using evoked response analysis in MEG and BOLD signal analysis in fMRI, represents an essential step toward an informed use of multimodal imaging that reaches beyond mere combination of location and timing of neural activation.