The disease often goes undiagnosed for several years, as it is sometimes not recognized and misdiagnosed as thrush or other problems and not correctly diagnosed until the patient is referred to a specialist when the problem does not clear up.

A biopsy of the affected skin can be done to confirm diagnosis. When a biopsy is done, hyperkeratosis, atrophic epidermis, sclerosis of dermis and lymphocyte activity in dermis are histological findings associated with LS. The biopsies are also checked for signs of dysplasia.

It has been noted that clinical diagnosis of LS can be "almost unmistakable" and therefore a biopsy may not be necessary.

Vaccinating girls with HPV vaccine before their initial sexual contact has been claimed to reduce incidence of VIN.

There are many other conditions that are similar in appearance and must be ruled out before a diagnosis of erythroplakia is made (see table). Sometimes, a diagnosis is delayed for up to two weeks in order to see if the lesion spontaneously regresses on its own or if another cause can be found. Erythroplakia frequently is associated with dysplasia, and is thus a precancerous lesion.

Treatment involves biopsy of the lesion to identify extent of dysplasia. Complete excision of the lesion is sometimes advised depending on the histopathology found in the biopsy. Even in these cases, recurrence of the erythroplakia is common and, thus, long-term monitoring is needed.

Gardasil 6 is an HPV vaccine aimed at preventing cervical cancers and genital warts. Gardasil is designed to prevent infection with HPV types 16, 18, 6, and 11. HPV types 16 and 18 currently cause about 70% of cervical cancer cases, and also cause some vulvar, vaginal, penile and anal cancers. HPV types 6 and 11 are responsible for 90% of documented cases of genital warts.

Gardasil 9, approved in 2014 protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

HPV vaccines do not currently protect against the virus strains responsible for plantar warts (verrucas).

The patient may have no symptoms, or local symptomatology including itching, burning, and pain.

The diagnosis is always based on a careful inspection and a targeted biopsy of a visible vulvar lesion.

The type and distribution of lesions varies among the two different types of VIN. In the Usual type VIN, seen more frequently in young patients, lesions tend to be multifocal over an otherwise normal vulvar skin. In the differentiated type VIN, usually seen in postmenopausal women, lesions tend to be isolated and are located over a skin with a vulvar dermatosis such as Lichen slerosus.

The diagnosis of genital warts is most often made visually, but may require confirmation by biopsy in some cases. Smaller warts may occasionally be confused with molluscum contagiosum.

Genital warts, histopathologically, characteristically rise above the skin surface due to enlargement of the dermal papillae, have parakeratosis and the characteristic nuclear changes typical of HPV infections (nuclear enlargement with perinuclear clearing).

DNA tests are available for diagnosis of high-risk HPV infections. Because genital warts are caused by low-risk HPV types, DNA tests cannot be used for diagnosis of genital warts or other low-risk HPV infections.

Some practitioners use an acetic acid solution to identify smaller warts ("subclinical lesions"), but this practice is controversial. Because a diagnosis made with acetic acid will not meaningfully affect the course of the disease, and cannot be verified by a more specific test, a 2007 UK guideline advises against its use.

Verruciform xanthoma is uncommon, with a female:male ratio of 1:1.1

The condition can be diagnosed based on inspection of the vulva. In patients with labial fusion, a flat plane of tissue with a dense central line of tissue is usually seen when the labia majora are retracted, while an anterior opening is usually present below the clitoris.

Common warts have a characteristic appearance under the microscope. They have thickening of the stratum corneum (hyperkeratosis), thickening of the stratum spinosum (acanthosis), thickening of the stratum granulosum, rete ridge elongation, and large blood vessels at the dermoepidermal junction.

The disease can last for a considerably long time. Occasionally, "spontaneous cure" may ensue, particularly in young girls.

Lichen sclerosus is associated with a higher risk of cancer. Skin that has been scarred as a result of lichen sclerosus is more likely to develop skin cancer. Women with lichen sclerosus may develop vulvar carcinoma. Lichen sclerosus is associated with 3–7% of all cases of vulvar squamous cell carcinoma. In women, it has been reported that 33.6 times higher vulvar cancer risk is associated with LS. A study in men reported that "The reported incidence of penile carcinoma in patients with BXO is 2.6–5.8%".

Differential diagnosis includes seborrheic keratosis, verruca simplex, condyloma acuminatum, granular cell myoblastoma, vulvar intraepithelial neoplasia, bowenoid papulosis, erythroplasia of Queyrat, and verrucous carcinoma

It is important to include that the lesion is associated with another cancer. A biopsy will establish the diagnosis. The histology of the lesion is the same as for Paget's disease of the breast.

Bowenoid papulosis is a cutaneous condition characterized by the presence of pigmented verrucous papules on the body of the penis. They are associated with human papillomavirus, the causative agent of genital warts. The lesions have a typical dysplastic histology and are generally considered benign, although a small percentage will develop malignant characteristics.

It is considered as a pre-malignant condition. Other terms used to describe the condition are: Erythroplasia of Queyrat, Squamous cell carcinoma in situ and Bowen’s disease. The term "Bowenoid papulosis" was coined in 1977 by Kopf and Bart and is named after dermatologist John Templeton Bowen.

The term “intraepithelial neoplasia” defines a premalignant intraepithelial change.

On the vulva it is termed VIN (vulvar or vulval intraepithelial neoplasia); on the penis, PIN (penile intraepithelial neoplasia); and on or around the anus, AIN (anal intraepithelial neoplasia). The terminology has been very confusing and it is now recommended that the terms Bowen’s disease, erythroplasia of Queyrat, and bowenoid papulosis should not be used for lesions in the anogenital area. However, dermatologists still recognize a distinct clinical variant, bowenoid papulosis, characterized by discrete papules in a younger age group and a tendency for spontaneous regression. Additionally, some authorities believe that erythroplasia of Queyrat and Bowen’s disease remain useful terms in men.

Treatment is not usually necessary in asymptomatic cases, since most fusions will separate naturally over time, but may be required when symptoms are present. The standard method of treatment for labial fusion is the application of topical estrogen cream onto the areas of adhesion, which is effective in 90% of patients. In severe cases where the labia minora are entirely fused, causing urinary outflow obstruction or vaginal obstruction, the labia should be separated surgically. Recurrence after treatment is common but is thought to be prevented by good hygiene practices. One study has shown that betamethasone may be more effective than estrogen cream in preventing recurrence, with fewer side effects.

Gardasil (sold by Merck & Co.) is a vaccine that protects against human papillomavirus types 6, 11, 16 and 18. Types 6 and 11 cause genital warts, while 16 and 18 cause cervical cancer. The vaccine is preventive, not therapeutic, and must be given before exposure to the virus type to be effective, ideally before the beginning of sexual activity. The vaccine is approved by the US Food and Drug Administration for use in both males and females as early as 9 years of age.

In the UK, Gardasil replaced Cervarix in September 2012 for reasons unrelated to safety. Cervarix had been used routinely in young females from its introduction in 2008, but was only effective against the high-risk HPV types 16 and 18, neither of which typically causes warts.

Warty dyskeratoma must be differentiated from vulvar dysplasia, Bowenoid papulosis, squamous carcinoma, condyloma, and other viral-induced squamous lesions.

The condition is one of exclusion and other vulvovaginal problems should be ruled out. The diagnosis is based on the typical complaints of the patient, essentially normal physical findings, and the absence of identifiable causes per the differential diagnosis. Cotton swab testing is used to differentiate between generalized and localized pain and delineate the areas of pain and categorize their severity. Patients often will describe the touch of a cotton ball as extremely painful, like the scraping of a knife. A diagram of pain locations may be helpful in assessing the pain over time. The vagina should be examined, and tests, including wet mount, vaginal pH, fungal culture, and Gram stain, should be performed as indicated. Fungal culture may identify resistant strains.

Many sufferers will see several doctors before a correct diagnosis is made. Many gynecologists are not familiar with this family of conditions, but awareness has spread with time. Sufferers are also often hesitant to seek treatment for chronic vulvar pain, especially since many women begin experiencing symptoms around the same time they become sexually active. Moreover, the absence of any visible symptoms means that before being successfully diagnosed many patients are told that the pain is "in their head".

Overall, five-year survival rates for vulvar cancer are around 78% but may be affected by individual factors including cancer stage, cancer type, patient age and general medical health. Five-year survival is greater than 90% for patients with stage I lesions but decreases to 20% when pelvic lymph nodes are involved. Lymph node involvement is the most important predictor of prognosis. Thus, early diagnosis is important.

Warty dyskeratoma, also known as an Isolated dyskeratosis follicularis, is a benign epidermal proliferation with distinctive histologic findings that may mimic invasive squamous cell carcinoma and commonly manifests as an umbilicated (Having a central mark or depression resembling a navel) lesion with a keratotic plug, WD have some histopathologic similarities to viral warts but it's not caused by HPV and the majority of these lesions display overall histopathologic features consistent with a follicular adnexal neoplasm. usually limited to the head, neck, scalp or face and vulva. Lesions are generally and sporadic and may be associated with a follicular unit. Oral involvement, particularly the hard palate, and genital involvement have been reported. it can also be thought of as one of the manifestations of focal acantholytic dyskeratosis, an epidermal reaction pattern that can be seen in several disorders, including Darier's disease and Grover's disease. But the main Difference between Darier disease and Warty dyskeratoma, is that Darier disease inherited dermatosis (autosomal dominant) consisting of multiple keratotic papules on the face, trunk, and extremities, while WD occurs as an isolated, noninherited, single keratotic nodule mainly confined to the head and neck as mentioned earlier.

Other cancerous lesions in the differential diagnosis include Paget's disease of the vulva and vulvar intraepithelial neoplasia (VIN). Non-cancerous vulvar diseases include lichen sclerosus, squamous cell hyperplasia, and vulvar vestibulitis. A number of diseases cause infectious lesions including herpes genitalis, human papillomavirus, syphilis, chancroid, granuloma inguinale, and lymphogranuloma venereum.

Paget's disease of the vulva, a rare disease, may be a primary lesion or associated with adenocarcinoma originating from local organs such as the Bartholin gland, the urethra, or the rectum and thus be secondary. Patients tend to be postmenopausal.

Paget's disease of the penis may also be primary or secondary, and is even rarer than genital Paget’s disease in women. At least one case has been misdiagnosed as Bowen's disease. Isolated Paget's disease of the penis is extremely rare.

Giant condyloma acuminatum (also known as a Buschke–Löwenstein tumor and "Giant condyloma of Buschke–Löwenstein tumor") is a rare cutaneous condition characterized by an aggressive, wart-like growth that is a verrucous carcinoma. It is attributed to human papillomavirus.

Diagnosis is readily made by the cotton-swab test, in which pressure is applied in a circular fashion around the vulvar vestibule to assess complaints of pain. Laboratory tests are used to exclude bacterial or viral infection, and a careful examination of the vulvo/vaginal area is conducted to assess whether any atrophy is present.

Due to the rarity of different types of vascular conditions, angiokeratomas may be misdiagnosed. A biopsy of the lesion can produce a more accurate diagnosis.