Motherless Brooklyn traces Lionel's growth from an orphaned child, to one of the Minna men, to an independent sleuth, to a legitimate car-service employee. The novel is in many ways a classic bildungsroman—a novel that deals with the formative years of an individual, that tells of the search for identity, truth, and sexual maturity. One of the central themes of the novel is Lionel's quest to discover his own identity, to find his place in the world as a real detective. Lionel's countless tics on his name are one way the novel represents this search; Liable Guesscog, Laughing Gassrog, Confessdog, Freakshow, Valiant Daffodil, Alibi Diffident, Final Escrow, Ironic Pissclaim are all, although apparently random verbal tics, representations of parts of Lionel's personality. Lionel's quest for Frank's killer also becomes Lionel's quest for his own identity. It is only through Frank's death that Lionel can become his own person; only through becoming Minna's avenger can Lionel become himself, a true detective at last. Lionel says at the beginning of the novel that "the distance between me and me was enormous"; through solving of the mystery of Frank's murder and through narrating the story, however, Lionel closes this gap. An important aspect of Lionel's self-discovery is his attempt to establish connections with others, symbolized at first by his possession of other people's cell phones and beepers. The novel moves from Lionel randomly answering other people's calls and messages to successfully establishing his own social relations, first with Kimmery and finally with Julia and the other Minna men.

The compulsion to play with language or the outbursts of Tourette's are clearly linked to Lionel's emotional states. One can see this in Minna's death scene, for example, which is punctuated by a sequence of jokes which themselves grow increasingly more punctuated by Lionel's Tourette's as he gets more upset. "Guy walks into the ambulance ramp stabs you in the goddamn emergency gut says I need an immediate stab in the garbage in the goddamn walk-in ambulance says just a minute looks in the back says I think I've got a stab in the goddamn walk-in immediate ambuloaf ambulamp octoloaf oafulope." In other words, Lionel's language expresses emotions in ways which "standard" language cannot. The punch line of the joke "I'm a frayed knot . . . I'm afrayed . . . we don't serve string" links joking—Lionel's way of communicating with Frank—to Lionel's feelings. Tourette's here becomes a way of expressing emotions that would be left unsaid otherwise, a way of connecting with other people.

Indeed, almost all of the major characters are involved in similar quests: Lionel, Julia, Gerard, and Kimmery are all searching for their own identities and their place in society. None of the major characters are who they appear to be: the Minna men are not really a car service, Julia is not really a tough-talking dame, Gerard is not a Roshi, and the Buddhists are a front for a money laundering operation. In fact, the Minna men are not really a detective agency either; they perform odd jobs for Frank Minna, but they do not know what they are doing or whom they are doing them for. In other words, even if the front of the car service is removed, there is another layer of deception underneath. Thus, the novel is both a mystery in which characters are not what they seem, and a quest story in which characters are seeking to discover who they really are. In the process of discovering who others really are (Gerard, Julia, the giant), Lionel discovers who he really is. The fact that Lionel does not discover his "true" identity in the sense of his true parents does not mean that he has not discovered a truth; indeed, what he discovers is that truth is layered, consists of layers of stories, of what Frank calls "wheels within wheels." In other words, the truth is a series of deceptions or stories, just as Lionel's "true" name is the series of variations his Tourette's produces. What Lionel discovers is that all identities are inventions of sorts; in the end, however, Lionel moves away from Frank's invention of him as "Freakshow" and Minna man; Lionel's individuation is represented as Lionel's move away from other people's inventions to his self-invention.

The novel follows Lionel's quest to become what he is merely pretending to be: first a detective, and then a car-service employee. Another important theme, and one that is closely linked to Lionel's quest to become a real detective, is the search for order. The Minna men have firmly established roles and routines while working together; they have learned a way to order their world with rhythm, language, habits, etc. Indeed, Motherless Brooklyn is all about social orders of various types, from the Minna men's patterned behavior to the Zen rituals Kimmery details for Lionel. In fact, the plot of the novel revolves around the Minna men's attempt to restore the order of their world, an order which was shattered by Frank's death. All of the characters are seeking to restore order to a world in which disorder has occurred. Detection is a primary way of restoring order—restoring order is not only what detectives in mysteries do, but is what mystery novels do for their readers.

At the same time that Tourette's represents being out-of-control, or disorder, it comes to represent this need or desire to order the world; in other words, Tourette's becomes the symbol of the theme of restoring order in the novel, a metaphor for detection and resolution. As Lionel describes it, Tourette's is a form of detecting and righting disorder: "The words rush out of the cornucopia of my brain to course over the surface of the world, tickling reality like fingers on piano keys. . . . They mean no harm. They placate, interpret, massage. Everywhere they're smoothing down imperfections, putting hairs in place, putting ducks in a row, replacing divots." One of the ways Lionel describes his Tourette's is as "just one big lifetime of tag, really. The world appoints me it, again and again. So I tag back." On one hand, this compulsion to verbalize, count, and touch interferes with Lionel's role as a detective; it is difficult for him to keep undercover. On the other hand, the obsessive-compulsiveness of Tourette's means Lionel does not let anything rest, anything go; that is, his Tourette's makes Lionel a superior detective. The "wheels within wheels" of Lionel's mind are always turning. Lionel's ability to see countless permutations or variations of events, personalities, and words is precisely what makes him a good detective; the fact that his mind is always processing makes him an ideal investigator: "Conspiracies are a version of Tourette's syndrome, the making and tracing of unexpected connections."

Another important theme in Motherless Brooklyn is the mystery of consciousness. Tourette's is one way of getting at the mystery of consciousness because it represents in such a dramatic fashion the dualism of the mind, the dualism Essrog alludes to when he talks about his "Tourette's brain" as if it were a separate character. "You're speaking without thinking" another character tells Lionel, calling attention to the gap between the subconscious and the conscious and the verbal. Lionel's ticcing connects the layers of the repressed, the thought, and the expressed. In this way, Tourette's comes to be a metaphor for the human condition—the dualism that exists for all of us between our exterior and interior lives, what Frank Minna calls the "wheels within wheels" of our minds. For the Buddhists in the novel, the achievement of "One Mind" is an overcoming duality of consciousness. For Lionel, however, it is sex which brings the two parts of his self together as well as conquering his Tourette's: "Sexual excitement stills my Tourette's brain . . . by setting up a deeper attentiveness in me, a finer vibration, which gathers and encompasses my urgent chaos, enlists it in a greater cause, like a chorus of voices somehow drawing a shriek into harmony. I'm still myself and still in myself, a rare and precious combination."

If Tourette's functions in Motherless Brooklyn as a metaphor for detection, it also functions as a metaphor for narrating. (Indeed, in classic detective fiction, the detective is the narrator, and the act of detecting and the act of telling the story are synonymous.) Tourette's is both the ultimate act of narrative and its opposite—it is both nonsense, and a way through which sense is trying to be made of the world. Tourette's can be seen as a sort of ultimate narrator or writer's symptom: a compulsion to rearrange words and language, to find as many different metaphors as possible to describe experience. In other words, if Tourette's represents narrating, it also comes to represent the acts of reading and writing. In fact, Lionel figures himself as a reader of the world "My mouth won't quit, though mostly I whisper or subvocalize like I'm reading aloud." Through reading Lionel's language, the reader him/herself becomes Tourettic—the novel implies further that all reading is a Tourettic act, as both involve processes of taking words and repeating them in patterns, and both involve a dualism of mind. A reader pieces together the narrative just as a detective pieces together a mystery.

If everything is Tourettic in Motherless Brooklyn, Tourette's is also everything. It is a metaphor for metaphorization itself, it is the wheel within the wheel. Even seeing Tourette's as a metaphor for metaphors is a sort of tic, a symptom of Tourette's itself. As Lionel says:

Have you noticed yet that I relate everything to my Tourette's? Yup, you guessed it, it's a tic. Counting is a symptom, but counting symptoms is also a symptom, a tick plus ultra. I've got meta-tourette's. Thinking about ticcing, my mind racing, thought reaching to touch every possible symptom. Touching touching. Counting counting. Thinking thinking. Mentioning mentioning Tourette's. It's sort of like talking about telephones over the telephone, or mailing letters describing the location of various mailboxes. Or like a tugboater whose favorite anecdote concerns actual tugboats.