Abstract Does the brain of a bilingual process language differently from that of a monolingual? We compared how bilinguals and monolinguals recruit classic language brain areas in response to a language task and asked whether there is a "neural signature" of bilingualism. Highly proficient and early-exposed adult Spanish-English bilinguals and English monolinguals participated. During functional magnetic resonance imaging (fMRI), participants completed a syntactic "sentence judgment task" [Caplan, D., Alpert, N., & Waters, G. Effects of syntactic structure and propositional number on patterns of regional cerebral blood flow. Journal of Cognitive Neuroscience, 10, 541-552, 1998]. The sentences exploited differences between Spanish and English linguistic properties, allowing us to explore similarities and differences in behavioral and neural responses between bilinguals and monolinguals, and between a bilingual's two languages. If bilinguals' neural processing differs across their two languages, then differential behavioral and neural patterns should be observed in Spanish and English. Results show that behaviorally, in English, bilinguals and monolinguals had the same speed and accuracy, yet, as predicted from the Spanish-English structural differences, bilinguals had a different pattern of performance in Spanish. fMRI analyses revealed that both monolinguals (in one language) and bilinguals (in each language) showed predicted increases in activation in classic language areas (e.g., left inferior frontal cortex, LIFC), with any neural differences between the bilingual's two languages being principled and predictable based on the morphosyntactic differences between Spanish and English. However, an important difference was that bilinguals had a significantly greater increase in the blood oxygenation level-dependent signal in the LIFC (BA 45) when processing English than the English monolinguals. The results provide insight into the decades-old question about the degree of separation of bilinguals' dual-language representation. The differential activation for bilinguals and monolinguals opens the question as to whether there may possibly be a "neural signature" of bilingualism. Differential activation may further provide a fascinating window into the language processing potential not recruited in monolingual brains and reveal the biological extent of the neural architecture underlying all human language.