Although not all people with Tourette's have comorbid conditions, most Tourette's patients presenting for clinical care at specialty referral centers may exhibit symptoms of other conditions along with their motor and phonic tics. Associated conditions include attention-deficit hyperactivity disorder (ADD or ADHD), obsessive–compulsive disorder (OCD), learning disabilities and sleep disorders. Disruptive behaviors, impaired functioning, or cognitive impairment in patients with comorbid Tourette's and ADHD may be accounted for by the comorbid ADHD, highlighting the importance of identifying and treating comorbid conditions. Disruption from tics is commonly overshadowed by comorbid conditions that present greater interference to the child. Tic disorders in the absence of ADHD do not appear to be associated with disruptive behavior or functional impairment, while impairment in school, family, or peer relations is greater in patients who have more comorbid conditions and often determines whether therapy is needed.

Because comorbid conditions such as OCD and ADHD can be more impairing than tics, these conditions are included in an evaluation of patients presenting with tics. "It is critical to note that the comorbid conditions may determine functional status more strongly than the tic disorder," according to Samuel Zinner, MD. The initial assessment of a patient referred for a tic disorder should include a thorough evaluation, including a family history of tics, ADHD, obsessive–compulsive symptoms, and other chronic medical, psychiatric and neurological conditions. Children and adolescents with TS who have learning difficulties are candidates for psychoeducational testing, particularly if the child also has ADHD. Undiagnosed comorbid conditions may result in functional impairment, and it is necessary to identify and treat these conditions to improve functioning. Complications may include depression, sleep problems, social discomfort, self-injury, anxiety, personality disorders, oppositional defiant disorder, and conduct disorders.

According to the fifth edition of the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-5), Tourette’s may be diagnosed when a person exhibits both multiple motor and one or more vocal tics over the period of a year; the motor and vocal tics need not be concurrent. The onset must have occurred before the age of 18, and cannot be attributed to the effects of another condition or substance (such as cocaine). Hence, other medical conditions that include tics or tic-like movements—such as autism or other causes of tourettism—must be ruled out before conferring a Tourette's diagnosis. Since 2000, the DSM has recognized that clinicians see patients who meet all the other criteria for Tourette's, but do not have distress or impairment.

There are no specific medical or screening tests that can be used in diagnosing Tourette's; it is frequently misdiagnosed or underdiagnosed, partly because of the wide expression of severity, ranging from mild (the majority of cases) or moderate, to severe (the rare, but more widely recognized and publicized cases). Coughing, eye blinking, and tics that mimic unrelated conditions such as asthma are commonly misdiagnosed.

The diagnosis is made based on observation of the individual's symptoms and family history, and after ruling out secondary causes of tic disorders. In patients with a typical onset and a family history of tics or obsessive–compulsive disorder, a basic physical and neurological examination may be sufficient.

There is no requirement that other comorbid conditions (such as ADHD or OCD) be present, but if a physician believes that there may be another condition present that could explain tics, tests may be ordered as necessary to rule out that condition. An example of this is when diagnostic confusion between tics and seizure activity exists, which would call for an EEG, or if there are symptoms that indicate an MRI to rule out brain abnormalities. TSH levels can be measured to rule out hypothyroidism, which can be a cause of tics. Brain imaging studies are not usually warranted. In teenagers and adults presenting with a sudden onset of tics and other behavioral symptoms, a urine drug screen for cocaine and stimulants might be necessary. If a family history of liver disease is present, serum copper and ceruloplasmin levels can rule out Wilson's disease. Most cases are diagnosed by merely observing a history of tics.

Secondary causes of tics (not related to inherited Tourette syndrome) are commonly referred to as tourettism. Dystonias, choreas, other genetic conditions, and secondary causes of tics should be ruled out in the differential diagnosis for Tourette syndrome. Other conditions that may manifest tics or stereotyped movements include developmental disorders, autism spectrum disorders, and stereotypic movement disorder; Sydenham's chorea; idiopathic dystonia; and genetic conditions such as Huntington's disease, neuroacanthocytosis, Hallervorden-Spatz syndrome, Duchenne muscular dystrophy, Wilson's disease, and tuberous sclerosis. Other possibilities include chromosomal disorders such as Down syndrome, Klinefelter syndrome, XYY syndrome and fragile X syndrome. Acquired causes of tics include drug-induced tics, head trauma, encephalitis, stroke, and carbon monoxide poisoning. The symptoms of Lesch-Nyhan syndrome may also be confused with Tourette syndrome. Most of these conditions are rarer than tic disorders, and a thorough history and examination may be enough to rule them out, without medical or screening tests.

Only about 10% of Tourette's patients exhibit coprolalia, but it tends to attract more attention than any other symptom. There is a paucity of epidemiological studies of Tourette syndrome; ascertainment bias affects clinical studies. Studies on people with Tourette's often "came from tertiary referral samples, the sickest of the sick". Further, the criteria for a diagnosis of Tourette's were changed in 2000, when the impairment criterion was removed from the DSM-IV-TR for all tic disorders, resulting in increased diagnoses of milder cases. Further, many clinical studies suffer from small sample size. These factors combine to render older estimates of coprolalia—biased towards clinical populations of the more severe cases—outdated. An international, multi-site database of 3,500 individuals with Tourette syndrome drawn from clinical samples found 14% of patients with Tourette's accompanied by comorbid conditions had coprolalia, while only 6% of those with uncomplicated ("pure") Tourette's had coprolalia. The same study found that the chance of having coprolalia increased linearly with the number of comorbid conditions: patients with four or five other conditions—in addition to tics—were four to six times more likely to have coprolalia than persons with only Tourette's. One study of a general pediatric practice found an 8% rate of coprolalia in children with Tourette syndrome, while another study found 60% in a tertiary referral center (where typically more severe cases are referred). A more recent Brazilian study of 44 patients with Tourette syndrome found a 14% rate of coprolalia; a Costa Rican study of 85 subjects found 20% had coprolalia; a Chilean study of 70 patients found an 8.5% rate of coprolalia; older studies in Japan reported a 4% incidence of coprolalia; and a still older clinical study in Brazil found 28% of 32 patients had coprolalia. Considering the methodological issues affecting all of these reports, the consensus of the Tourette Syndrome Association is that the actual number is below 15 percent.

Coprolalia encompasses words and phrases that are culturally taboo or generally unsuitable for acceptable social use, when used out of context. The term is not used to describe contextual swearing. It is usually expressed out of social or emotional context, and may be spoken in a louder tone or different cadence or pitch than normal conversation. It can be a single word, or complex phrases. A person with coprolalia may repeat the word mentally rather than saying it out loud; these subvocalizations can be very distressing.

Coprolalia is an occasional characteristic of Tourette syndrome, although it is not required for a diagnosis of Tourette's. In Tourette syndrome, compulsive swearing can be uncontrollable and undesired by the person uttering the phrases. Involuntary outbursts, such as racial or ethnic slurs in the company of those most offended by such remarks, can be particularly embarrassing. The phrases uttered by a person with coprolalia do not necessarily reflect the thoughts or opinions of the person.

Cases of deaf Tourette patients swearing in sign language have been described, showing that coprolalia is not just a consequence of the short and sudden sound pattern of many swear words.

Palilalia (from the Greek πάλιν ("pálin") meaning "again" and λαλιά ("laliá") meaning "speech" or "to talk"), a complex tic, is a language disorder characterized by the involuntary repetition of syllables, words, or phrases. It has features resembling other complex tics such as echolalia or coprolalia, but, unlike other aphasias, palilalia is based upon contextually correct speech.

It was originally described by Alexandre-Achille Souques in a patient with stroke that resulted in left-side hemiplegia, although a condition described as auto-echolalia in 1899 by Édouard Brissaud may have been the same condition.

Copropraxia is a tic consisting of involuntarily performing obscene or forbidden gestures, or inappropriate touching. Copropraxia comes from the Greek "κόπρος" meaning "feces" and "πράξις" meaning "action". Copropraxia is a rare characteristic of Tourette syndrome.

Related terms are coprolalia, referring to involuntary usage of profane words, and coprographia, making vulgar writings or drawings.

Palilalia is considered an aphasia, a disorder of language, and is not to be confused with speech disorders, as there is no difficulty in the formation of internal speech. Palilalia is similar to speech disorders such as stuttering or cluttering, as it tends to only express itself in spontaneous speech, such as answering basic questions, and not in automatic speech such as reading or singing; however, it distinctively affects words and phrases rather than syllables and sounds.

Palilalia may occur in conditions affecting the pre-frontal cortex or basal ganglia regions, either from physical trauma, neurodegenerative disorders, genetic disorders, or a loss of dopamine in these brain regions. Palilalia occurs most commonly in Tourette syndrome and may be present in neurodegenerative disorders like Alzheimer's disease and progressive supranuclear palsy.

Coprographia is involuntarily making vulgar writings or drawings. Coprographia comes from the Greek "κόπρος" meaning "feces" and "graphia" meaning to write.

Related terms are coprolalia, the involuntary usage of scatalogical words, and copropraxia, the involuntary performance of obscene gestures.

The use of biochemical testing for the detection of carriers is technically demanding and not often used. Biochemical analyses that have been performed on hair bulbs from at risk women have had a small number of both false positive and false negative outcomes. If only a suspected carrier female is available for mutation testing, it may be appropriate to grow her lymphocytes in 6-thioguanine (a purine analogue), which allows only HGPRT-deficient cells to survive. A mutant frequency of 0.5–5.0 × 10 is found in carrier females, while a non-carrier female has a frequency of 1–20 × 10. This frequency is usually diagnostic by itself.

Molecular genetic testing is the most effective method of testing, as HPRT1 is the only gene known to be associated with LNS. Individuals who display the full Lesch–Nyhan phenotype all have mutations in the HPRT1 gene. Sequence analysis of mRNA is available clinically and can be utilized in order to detect HPRT1 mutations in males affected with Lesch–Nyhan syndrome. Techniques such as RT-PCR, multiplex genomic PCR, and sequence analysis (cDNA and genomic DNA), used for the diagnosis of genetic diseases, are performed on a research basis. If RT-PCR tests result in cDNA showing the absence of an entire exon or exons, then multiplex genomic PCR testing is performed. Multiplex genomic PCR testing amplifies the nine exons of the HPRT1 gene as eight PCR products. If the exon in question is deleted, the corresponding band will be missing from the multiplex PCR. However, if the exon is present, the exon is sequenced to identify the mutation, therefore causing exclusion of the exon from cDNA. If no cDNA is created by RT-PCR, then multiplex PCR is performed on the notion that most or all of the gene is obliterated.

The urate to creatinine (breakdown product of creatine phosphate in muscle) concentration ratio in urine is elevated. This is a good indicator of acid overproduction. For children under ten years of age with LNS, a urate to creatinine ratio above two is typically found. Twenty-four-hour urate excretion of more than 20 mg/kg is also typical but is not diagnostic. Hyperuricemia (serum uric acid concentration of >8 mg/dL) is often present but not reliable enough for diagnosis. Activity of the HGPRT enzyme in cells from any type of tissue (e.g., blood, cultured fibroblasts, or lymphoblasts) that is less than 1.5% of normal enzyme activity confirms the diagnosis of Lesch–Nyhan syndrome. Molecular genetic studies of the HPRT gene mutations may confirm diagnosis, and are particularly helpful for subsequent 'carrier testing' in at-risk females such as close family relatives on the female side.