《我的天才女友》是埃莱娜·费兰特“那不勒斯四部曲”的第一部，讲述了两个女主人公莉拉和埃莱娜的少女时代。故事一开始，已经功成名就的埃莱娜接到莉拉儿子里诺的电话，说他母亲彻底消失了。埃莱娜想起莉拉对自己命运的预言，于是她写下她们一生的故事……
莉拉和埃莱娜一起成长于那不勒斯一个破败的社区，从小形影不离，彼此信赖，但又都视对方为自己隐秘的镜子，暗暗角力。莉拉聪明，漂亮。她可以毫不畏惧地和欺凌自己的男生对质，也可以去找人人惧怕的阿奇勒﹒卡拉奇要回被他夺走的玩具；埃莱娜既羡慕莉拉的学习天赋和超人的决断力，又一直暗暗模仿莉拉。
家人不支持莉拉继续求学，因此她到父亲和兄长苦苦维持的修鞋店帮工，又面临几个纨绔子弟的追求。埃莱娜则怀着对朋友的关爱、嫉妒和理解，独自继续学业，却始终无法面对和莉拉竞争的失落。
最终，十六岁的莉拉决定嫁给肉食店老板，但在婚宴上，她发现了丈夫的背叛。而埃莱娜也站在成人世界的入口，既为前途担忧，也因对思想前卫的尼诺产生朦胧好感而彷徨。
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