Lexical semantic ambiguity is the phenomenon when a word has multiple meanings (e.g. ‘bank’). The aim of this event-related functional MRI study was to identify those brain areas, which are involved in contextually driven ambiguity resolution. Ambiguous words were selected which have a most frequent, dominant, and less frequent, subordinate meaning. These words were presented in two types of sentences: (1) a sentence congruent with the dominant interpretation and (2) a sentence congruent with the subordinate interpretation. Sentences without ambiguous words served as a control condition. The ambiguous words always occurred early in the sentences and were biased towards one particular meaning by the final word(s) of the sentence; the event at the end of the sentences was modeled. The results indicate that a bilaterally distributed network supports semantic ambiguity comprehension: left (BA 45/44) and right (BA 47) inferior frontal gyri and left (BA 20/37) and right inferior/middle temporal gyri (BA 20). The pattern of activation is most consistent with a scenario in which initially a frequency-based probabilistic choice is made between the alternative meanings, and the meaning is updated when this interpretation does not fit into the final disambiguating context. The neural pattern is consistent with the results of other neuroimaging experiments which manipulated various aspects of integrative and context processing task demands. The presence of a bilateral network is also in line with the lesion and divided visual field literature, but contrary to earlier claims, the two hemispheres appear to play similar roles during semantic ambiguity resolution.