Second language (L2) acquisition necessitates learning and retrieving new words in different modes. In this study, we attempted to investigate the cortical representation of an L2 vocabulary acquired in different learning modes and in cross-modal transfer between learning and retrieval. Healthy participants learned new L2 words either by written translations (text-based learning) or in real-life situations (situation-based learning). Brain activity was then measured during subsequent retrieval of these words. The right supramarginal gyrus and left middle frontal gyrus were involved in situation-based learning and text-based learning, respectively, whereas the left inferior frontal gyrus was activated when learners used L2 knowledge in a mode different from the learning mode. Our findings indicate that the brain regions that mediate L2 memory differ according to how L2 words are learned and used.