Visual diagnosis is made by the "stuck on" appearance, horny pearls or cysts embedded in the structure. Darkly pigmented lesions can be challenging to distinguish from nodular melanomas. Furthermore, thin seborrheic keratoses on facial skin can be very difficult to differentiate from lentigo maligna even with dermatoscopy. Clinically, epidermal nevi are similar to seborrheic keratoses in appearance. Epidermal nevi are usually present at or near birth. Condylomas and warts can clinically resemble seborrheic keratoses, and dermatoscopy can be helpful. On the penis and genital skin, condylomas and seborrheic keratoses can be difficult to differentiate, even on biopsy.

To date, the gold standard in the diagnosis of seborrheic keratosis is represented by the histolopathologic analysis of a skin biopsy.

Tissue biopsy is usually indicated to rule out other causes of white patches and also to enable a detailed histologic examination to grade the presence of any epithelial dysplasia. This is an indicator of malignant potential and usually determines the management and recall interval. The sites of a leukoplakia lesion that are preferentially biopsied are the areas that show induration (hardening) and erythroplasia (redness), and erosive or ulcerated areas. These areas are more likely to show any dysplasia than homogenous white areas.

Brush biopsy/exfoliative cytology is an alternative to incisional biopsy, where a stiff brush is scraped against the lining of the mouth to remove a sample of cells. This is then made into a smear which can be examined microscopically. Sometimes the biopsy site can be selected with adjunct methods which aim to highlight areas of dysplasia. Toluidine blue staining, where the dye is preferentially retained by dysplastic tissue, is sometimes used, but there is high false positive rate. Other methods involve the use of illuminescence, relying on either the property of normal autoflorescent molecules in mucosa such as collagen and keratin which is lost from areas of dysplasia or carcinoma under blue light, or by initially staining of the mucosa with toluidine blue or dilute acetic acid and examination under white light.

Keratoacanthoma presents as a fleshy, elevated and nodular lesion with an irregular crater shape and a characteristic central hyperkeratotic core. Usually the patient will notice a rapidly growing dome-shaped tumor on sun-exposed skin.

If the entire lesion is removed, the pathologist will probably be able to differentiate between keratoacanthoma and squamous cell carcinoma. If only part of the lesion is removed, confident diagnosis may be impossible.

No treatment of seborrheic keratoses is necessary, except for aesthetic reasons. Since a slightly increased risk of localized infection caused by picking at the lesion has been described, if a lesion becomes itchy or irritated by clothing or jewelry, a surgical excision is generally recommended.

Small lesions can be treated with light electrocautery. Larger lesions can be treated with electrodesiccation and curettage, shave excision, or cryosurgery. When correctly performed, removal of seborrheic keratoses will not cause much visible scarring except in persons with dark skin tones.

Excision of the entire lesion, with adequate margin, will remove the lesion, allow full tissue diagnosis, and leave a planned surgical wound which can usually be repaired with a good cosmetic result. However, removing the entire lesion (especially on the face) may present difficult problems of plastic reconstruction. (On the nose and face, Mohs surgery may allow for good margin control with minimal tissue removal, but many insurance companies require the definitive diagnosis of a malignancy "before" they are prepared to pay the extra costs of Mohs surgery.) Especially in more cosmetically-sensitive areas, and where the clinical diagnosis is reasonably certain, alternatives to surgery may include no treatment (awaiting spontaneous resolution).

On the trunk, arms, and legs, electrodesiccation and curettage often suffice to control keratoacanthomas until they regress. Other modalities of treatment include cryosurgery and radiotherapy; intralesional injection of methotrexate or of 5-fluorouracil have also been used.

Recurrence after electrodesiccation and curettage can occur; it can usually be identified and treated promptly with either further curettage or surgical excision.

The annual malignant transformation rate of leukoplakia rarely exceeds 1%, i.e. the vast majority of oral leukoplakia lesions will remain benign. A number of clinical and histopathologic features are associated with varying degrees of increased risk of malignant transformation, although other sources argue that there are no universally accepted and validated factors which can reliably predict malignant change. It is also unpredictable to an extent if an area of leukoplakia will disappear, shrink or remain stable.

- Presence and degree of dysplasia (mild, moderate or severe/carcinoma in situ). Dysplasia is the most important predictor of malignant change, and about 10% of leukoplakia lesions show dysplasia when biopsied.

- Leukoplakia located on the floor of the mouth, the posterior and lateral tongue, and the retromolar areas (the region behind the wisdom teeth) have higher risk, whereas white patches in areas such as the top surface of the tongue and the hard palate do not have significant risk. Although these "high risk" sites are recognized, statistically, leukoplakia is more common on the buccal mucosa, alveolar mucosa, and the lower labial mucosa. Leukoplakia of the floor of the mouth and tongue accounts for over 90% of leukoplakias showing dysplasia or carcinoma on biopsy. This is thought to be due to pooling of saliva in the lower part of the mouth, exposing these areas to more carcinogens held in suspension.

- Red lesions (erythroplasia) and mixed red and white lesions (erythroleukoplakia/"speckled leukoplakia") have a higher risk of malignant change than homogenous leukoplakia.

- Verrucous or nodular areas have a higher risk.

- Although smoking increases risk of malignant transformation, smoking also causes many white patches with no dysplasia. This means that statistically, white patches in non smokers have a higher risk.

- Older people with white patches are at higher risk.

- Larger white patches are more likely to undergo malignant transformation than smaller lesions.

- White patches which have been present for a long period of time have higher risk.

- Persons with a positive family history of cancer in the mouth.

- Candida infection in the presence of dysplasia has a small increased risk.

- A change in the appearance of the white patch, apart from a change in the color, has a higher risk. Changes in the lesion such as becoming fixed to underlying tissues, ulceration, cervical lymphadenopathy (enlargement of lymph nodes in the neck), and bone destruction may herald the appearance of malignancy.

- White patches present in combination with other conditions that carry a higher risk (e.g. oral submucous fibrosis), are more likely to turn malignant.

- Although overall, oral cancer is more common in males, females with white patches are at higher risk than men.

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.

Oral propranolol appears to be the most effective treatment for reducing the size of capillary hemangiomas in children and is more effective than placebo, observation without intervention, or oral corticosteroids.

Angiokeratoma may be classified as:

- "Angiokeratoma of Mibelli" (also known as "Mibelli's angiokeratoma," "Telangiectatic warts") consists of 1- to 5-mm red vascular papules, the surfaces of which become hyperkeratotic in the course of time. The disease is named after Italian dermatologist Vittorio Mibelli (1860-1910).

- "Angiokeratoma of Fordyce" (also known as "Angiokeratoma of the scrotum and vulva," though not to be confused with Fordyce's spots) is a skin condition characterized by red to blue papules on the scrotum or vulva.

- "Solitary angiokeratoma" is a small, bluish-black, warty papule that occurs predominantly on the lower extremities.

- "Verrucous vascular malformation" (also known as "Angiokeratoma circumscriptum naeviforme") is a malformation of dermal and subcutaneous capillaries and veins, a congenital vascular malformation, which, over time, a verrucous component appears.

Due to its overwhelming incidence on the gingiva, the condition is often associated with two other diseases, though not because they occur together. Instead, the three are associated with each other because they appear frequently on gingiva—peripheral giant cell granuloma and peripheral ossifying fibroma. Detailed analysis can be used to distinguish these conditions.

Prognosis is usually good, however recurrence may happen with rate up to 16%. Presence of myxoid structures in the pyogenic granuloma may be the main cause of recurrence.

Although pyogenic granulomas are not infectious or malignant, treatment may be considered because of bleeding or ulceration. Frequently, pyogenic granulomas are treated with electrodesiccation (cauterization) and curettage (excision), though laser treatment using pulsed dye laser or CO laser is often effective.

Several reports have demonstrated the efficacy of topical application of the beta-adrenergic antagonist timolol in the treatment of pediatric pyogenic granuloma.

There is usually no treatment if the pyogenic granuloma occurs during pregnancy since the lesion may heal spontaneously. Recurrent bleeding in either oral or nasal lesions may necessitate excision and cauterization sooner, however. If aesthetics are a concern, then treatment may be pursued as well. Usually, only minor surgery may be needed, along with a dental cleaning for oral lesions to remove any calculus or other source of irritation. For nasal lesions, nose-picking should be discouraged.

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

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

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

Linear verrucous epidermal nevus (also known as a "Linear epidermal nevus," and "Verrucous epidermal nevus") is a skin lesion characterized by a verrucous skin-colored, dirty-gray or brown papule. Generally, multiple papules present simultaneously, and coalesce to form a serpiginous plaque. When this nevus covers a diffuse or extensive portion of the body's surface area, it may be referred to as a systematized epidermal nevus, when it involved only one-half of the body it is called a nevus unius lateris.

Isthmicoma (also known as "Infundibuloma," and "Tumor of the follicular infundibulum") are a cutaneous condition characterized by flat, keratotic papules of the head and neck, skin lesions that are usually solitary.

Dermatofibromas are hard solitary slow-growing papules (rounded bumps) that may appear in a variety of colours, usually brownish to tan; they are often elevated or pedunculated. A dermatofibroma is associated with the dimple sign; by applying lateral pressure, there is a central depression of the dermatofibroma. Although typical dermatofibromas cause little or no discomfort, itching and tenderness can occur. Dermatofibromas can be found anywhere on the body, but most often they are found on the legs and arms. They occur most often in women; the male to female ratio is about 1:4. The age group in which they most commonly occur is 20 to 45 years.

Some physicians and researchers believe dermatofibromas form as a reaction to previous injuries such as insect bites or thorn pricks. They are composed of disordered collagen laid down by fibroblasts. Dermatofibromas are classed as benign skin lesions, meaning they are completely harmless, though they may be confused with a variety of subcutaneous tumours. Deep penetrating dermatofibromas may be difficult to distinguish, even histologically, from rare malignant fibrohistocytic tumours like dermatofibrosarcoma protuberans.

Dermatofibromas typically have a positive "buttonhole sign", or central dimpling in the center.

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.

Usually, a common form of treatment for the condition is a type of hand cream which moisturises the hard skin. However, currently the condition is incurable.

Porokeratosis is a specific disorder of keratinization that is characterized histologically by the presence of a cornoid lamella, a thin column of closely stacked, parakeratotic cells extending through the stratum corneum with a thin or absent granular layer.

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.

The treatment for CGCG is thorough curettage. A referral is made to an oral surgeon. Recurrence ranges from 15%–20%. In aggressive tumors, three alternatives to surgery are undergoing investigation:

- corticosteroids;

- calcitonin (salmon calcitonin);

- interferon α-2a.

These therapeutic approaches provide positive possible alternatives for large lesions. The long term prognosis of giant-cell granulomas is good and metastases do not develop.

Benign fibrous histiocytomas (also known as dermal dendrocytoma, dermatofibroma, fibrous dermatofibroma, fibrous histiocytoma, fibroma simplex, nodular subepidermal fibrosis, and sclerosing hemangioma) are benign skin growths.

Angiolymphoid hyperplasia with eosinophilia (also known as: "Epithelioid hemangioma," "Histiocytoid hemangioma," "Inflammatory angiomatous nodule," "Intravenous atypical vascular proliferation," "Papular angioplasia," "Inflammatory arteriovenous hemangioma," and "Pseudopyogenic granuloma") usually presents with pink to red-brown, dome-shaped, dermal papules or nodules of the head or neck, especially about the ears and on the scalp.

It, or a similar lesion, has been suggested as a feature of IgG4-related skin disease, which is the name used for skin manifestations of IgG4-related disease.

Microvenular hemangioma (also known as "Microcapillary hemangioma") is an acquired benign vascular neoplasm that presents as an asymptomatic, slowly growing, 0.5- to 2.0 cm reddish lesion on the forearms or other sites of young to middle-aged adults.