The most important scene in The Fortress of Solitude by Jonathan Lethem would reflect a personal choice and it really is up to the reader to decide which, for him or her, is most significant.
From the beginning of the book, the reader may be inclined to choose the scene between Isabel and Rachel, Dylan's mother, where Rachel sets forth her reasons for choosing to send Dylan to public school. Rachel suggests that “It’s a problem for him to solve, school. I did it, so can he.” This resonates her whole attitude towards child-rearing and will affect Dylan enormously as he will, later in life, apportion blame on his parents' lack of parenting.
Later, Dylan's girlfriend recognizes that he is distant and retreats into thoughts of his childhood - that "privileged sanctuary" - instead of concentrating on his life with her and his future. He ponders that, “My childhood is the only part of my life that wasn't, uh, overwhelmed by my childhood.” Again this is significant because the issues surrounding Dylan's childhood are again at odds with his ability to move forward with his life in a positive manner.
Another relevant scene could be when Dylan, still drunk from the night before, goes to his father's screening and he refers to his ability to remain unseen - even in a crowd; "I'd become a skilled invisible man ten years before..." In his hallucinatory state, Dylan is glad to be "invisible" and the reader is certain of his feelings of being apart and isolated from the rest and the fact that he has always felt this way.
At the end of the story, Dylan reminds the reader that his childhood was not good and that his parents were neglectful: " Abraham was the father I never had, and Rachel was the mother I never had." This quote is important in understanding the themes of the novel as Dylan has always blamed his parents for not giving him what he needed and now, as the story ends, Dylan is more accepting of his father's ways , as he drives him home, "calm for an instant, settled in our task." This is really the first step towards acceptance for Dylan and will allow him to move forward.