The disorder typically appears among young girls and adolescents but cases in children as young as 17 months have been reported.

The thickness of the mucosa may be an important factor in aphthous stomatitis. Usually, ulcers form on the thinner, non-keratinizing mucosal surfaces in the mouth. Factors which decrease the thickness of mucosa increase the frequency of occurrence, and factors which increase the thickness of the mucosa correlate with decreased ulceration.

The nutritional deficiencies associated with aphthous stomatitis (B12, folate, and iron) can all cause a decrease in the thickness of the oral mucosa (atrophy).

Local trauma is also associated with aphthous stomatitis, and it is known that trauma can decrease the mucosal barrier. Trauma could occur during injections of local anesthetic in the mouth, or otherwise during dental treatments, frictional trauma from a sharp surface in the mouth such as broken tooth, or from tooth brushing.

Hormonal factors are capable of altering the mucosal barrier. In one study, a small group of females with apthous stomatitis had fewer occurrences of aphthous ulcers during the luteal phase of the menstrual cycle or with use of the contraceptive pill. This phase is associated with a fall in progestogen levels, mucosal proliferation and keratinization. This subgroup often experiences remission during pregnancy. However, other studies report no correlation between aphthous stomatitis and menstrual period, pregnancy or menopause.

Aphthous stomatitis is common in people who smoke, and there is also a correlation between habit duration and severity of the condition. Tobacco use is associated with an increase in keratinization of the oral mucosa. In extreme forms, this may manifest as leukoplakia or stomatitis nicotina (smoker's keratosis). This increased keratinization may mechanically reinforce the mucosa and reduce the tendency of ulcers to form after minor trauma, or present a more substantial barrier to microbes and antigens, but this is unclear. Nicotine is also known to stimulate production of adrenal steroids and reduce production of TNF-α, interleukin-1 and interleukin-6. Smokeless tobacco products also seem to protect against aphthous stomatitis. Cessation of smoking is known to sometimes precede the onset of aphthous stomatitis in people previously unaffected, or exacerbate the condition in those who were already experiencing aphthous ulceration. Despite this correlation, starting smoking again does not usually lessen the condition.

Various antigenic triggers have been implicated as a trigger, including L forms of streptococci, herpes simplex virus, varicella-zoster virus, adenovirus, and cytomegalovirus. Some people with aphthous stomatitis may show herpes virus within the epithelium of the mucosa, but without any productive infection. In some persons, attacks of ulceration occur at the same time as asymptomatic viral shedding and elevated viral titres.

In some instances, recurrent mouth ulcers may be a manifestation of an allergic reaction. Possible allergens include certain foods ("e.g.", chocolate, coffee, strawberries, eggs, nuts, tomatoes, cheese, citrus fruits, benzoates, cinnamaldehyde, and highly acidic foods), toothpastes, and mouthwashes. Where dietary allergens are responsible, mouth ulcers usually develop within about 12–24 hours of exposure.

Sodium lauryl sulphate (SLS), a detergent present in some brands of toothpaste and other oral healthcare products, may produce oral ulceration in some individuals. It has been shown that aphthous stomatitis is more common in people using toothpastes containing SLS, and that some reduction in ulceration occurs when a SLS-free toothpaste is used. Some have argued that since SLS is almost ubiquitously used in oral hygiene products, there is unlikely to be a true predisposition for aphthous stomatitis caused by SLS.

Many infections can cause oral ulceration (see table). The most common are herpes simplex virus (herpes labialis, primary herpetic gingivostomatitis), varicella zoster (chicken pox, shingles), and coxsackie A virus (hand, foot and mouth disease). Human immunodeficiency virus (HIV) creates immunodeficiencies which allow opportunistic infections or neoplasms to proliferate. Bacterial processes leading to ulceration can be caused by "Mycobacterium tuberculosis" (tuberculosis) and "Treponema pallidum" (syphilis).

Opportunistic activity by combinations of otherwise normal bacterial flora, such as aerobic streptococci, "Neisseria", "Actinomyces", spirochetes, and "Bacteroides" species can prolong the ulcerative process. Fungal causes include "Coccidioides immitis" (valley fever), "Cryptococcus neoformans" (cryptococcosis), and "Blastomyces dermatitidis" ("North American Blastomycosis"). Entamoeba histolytica, a parasitic protozoan, is sometimes known to cause mouth ulcers through formation of cysts.

Many drugs can cause mouth ulcers as a side effect. Common examples are alendronate (a bisphosphonate, commonly prescribed for osteoporosis), cytotoxic drugs (e.g. methotrexate, i.e. chemotherapy), non-steroidal anti-inflammatory drugs, nicorandil (may be prescribed for angina) and propylthiouracil (e.g. used for hyperthyroidism). Some recreational drugs can cause ulceration, e.g. cocaine.

The wounds from which ulcers arise can be caused by a wide variety of factors, but the main cause is impaired blood circulation. Especially, chronic wounds and ulcers are caused by poor circulation, either through cardiovascular issues or external pressure from a bed or a wheelchair. A very common and dangerous type of skin ulcers are caused by what are called pressure-sensitive sores, more commonly called bed sores and which are frequent in people who are bedridden or who use wheelchairs for long periods. Other causes producing skin ulcers include bacterial or viral infections, fungal infections and cancers. Blood disorders and chronic wounds can result in skin ulcers as well.

Venous leg ulcers due to impaired circulation or a blood flow disorder are more common in the elderly.

Lipschütz ulcer, ulcus vulvae acutum or reactive non-sexually related acute genital ulcers () is a rare disease characterized by painful genital ulcers, fever, and lymphadenopathy, occurring most commonly, but not exclusively, in adolescents and young women. Previously, it was described as being more common in virgins. It is not a sexually transmitted disease, and is often misdiagnosed, sometimes as a symptom of Behçet's disease.

Lipschütz ulcer is named after Benjamin Lipschütz, who first described it in 1912. The cause is still unknown, although it has been associated with several infectious causes, including paratyphoid fever, cytomegalovirus, "Mycoplasma pneumoniae" and Epstein-Barr virus infection

Among those in the intensive care unit, ulceration resulting in bleeding is very rare.

Pressure ulcers can trigger other ailments, cause considerable suffering, and can be expensive to treat. Some complications include autonomic dysreflexia, bladder distension, bone infection, pyarthroses, sepsis, amyloidosis, anemia, urethral fistula, gangrene and very rarely malignant transformation (Marjolin's ulcer - secondary carcinomas in chronic wounds). Sores may recur if those with pressure ulcers do not follow recommended treatment or may instead develop seromas, hematomas, infections, or wound dehiscence. Paralyzed individuals are the most likely to have pressure sores recur. In some cases, complications from pressure sores can be life-threatening. The most common causes of fatality stem from kidney failure and amyloidosis.

Pressure ulcers are also painful, with individuals of all ages and all stages of pressure ulcers reporting pain.

There are over 100 risk factors for pressure ulcers. Factors that may place a patient at risk include immobility, diabetes mellitus, peripheral vascular disease, malnutrition, cerebral vascular accident and hypotension. Other factors are age of 70 years and older, current smoking history, dry skin, low body mass index, urinary and fecal incontinence, physical restraints, malignancy, and history of pressure ulcers.

Different types of discharges from ulcer are:

- Serous, usually seen in healing ulcer

- Purulent, seen in infected ulcer. Yellow creamy discharge is observed in staphylococcal infection; bloody opalescent discharge in streptococcal infection, while greenish discharge is seen in pseudomonas ulcer

- Bloody (sanguineous), usually seen in malignant ulcers and in healing ulcers with healthy granulation tissue

- Seropurulent

- Serosanguinous

- Serous with sulphur granules, seen in actinomycosis

- Yellowish, as seen in tuberculous ulcer

The exact cause of the condition is unknown. There is most evidence to support vascular infarction and ischemic necrosis of salivary gland lobules as a mechanism for the condition. Experimentally, local anaesthetic injections and tying of the arteries is reported to trigger the development of tissue changes similar to NS in lab rats. Factors which are thought to cause this ischemia are listed below, however sometimes there is no evident predisposing factor or initiating event.

- Trauma e.g. during intubation, or surgical procedures

- Local anesthetic injection

- Smoking

- Alcohol

- Diabetes mellitus

- Vascular disease, (e.g. arteriosclerosis)

- Pressure from a dental prosthesis

- Allergy

- Bulimia

- Infection

- Ionizing radiation

There is now considerable evidence to suggest that this disease is an infection. "Mycobacterium ulcerans" has recently been isolated from lesions and is unique to tropical ulcers. Early lesions may be colonized or infected by, "Bacillus fusiformis" (Vincent's organism), anaerobes and spirochaetes. Later, tropical ulcer may become infected with a variety of organisms, notably, staphylococci and/or streptococci. The condition has been shown to be transmissible by inoculation of material from affected patients.

A recent retrospective study of all cases of Ecthyma gangrenosum from 2004-2010 in a university hospital in Mexico shows that neutropenia in immunocompromised patients is the most common risk factor for ecthyma gangrenosum.

Risk factors for stress ulcer formation that have been identified are numerous and varied. However, two landmark studies and one position paper exist that addresses the topic of risk factors for stress ulcer formation:

- Non-critically ill medical patients with 2 or more of the following: respiratory failure, sepsis, heart failure, hepatic encephalopathy, jaundice, kidney failure, stroke, hypertension, previous gastrointestinal disease and treatment with corticosteroids, NSAIDS, heparin, or warfarin.

- In surgical critically ill patients, only those patients who are on a mechanical ventilator for more than 48 hours and/or those with a coagulopathy.

- The American Society of Health-System Pharmacists guideline recommends against the practice of stress ulcer prophylaxis in non-critically ill patients.

Adequate footwear is important to prevent trauma. General good health and nutrition also reduce ulcer risk. Adequate and prompt cleansing and treatment of ankle and leg skin breaks is also important. Improving hygiene and nutrition may help to prevent tropical ulcers.

The drug Elmiron helps, for some patients, to prevent the formation of Hunner's Ulcers by coating the bladder wall, thus making it harder for the acid in urine to irritate the bladder wall lining, which can lead to ulceration. (not cited)

This condition results from denervation of areas exposed to day-to-day friction of bony prominences. The denervation may be result of any of the following diseases:

- Spinal injuries

- Leprosy

- Peripheral nerve injury

- Diabetic neuropathy

- Tabes dorsalis

- Transverse myelitis

- Meningomyelocele

Compression stockings appear to prevent the formation of new ulcers in people with a history of venous ulcers.

More than 70% of cases are recorded in people with at least one of the following clinical situations: immunosuppression, diabetes, alcoholism/drug abuse/smoking, malignancies, and chronic systemic diseases. For reasons that are unclear, it occasionally occurs in people with an apparently normal general condition.

The infection begins locally at a site of trauma, which may be severe (such as the result of surgery), minor, or even non-apparent.

Corneal ulcer, or ulcerative keratitis, is an inflammatory or more seriously, infective condition of the cornea involving disruption of its epithelial layer with involvement of the corneal stroma. It is a common condition in humans particularly in the tropics and the agrarian societies. In developing countries, children afflicted by Vitamin A deficiency are at high risk for corneal ulcer and may become blind in both eyes, which may persist lifelong. In ophthalmology, a corneal ulcer usually refers to having an infectious cause while the term corneal abrasion refers more to physical abrasions.

Chancroid is a bacterial infection caused by the fastidious Gram-negative streptobacillus "Haemophilus ducreyi". It is a disease found primarily in developing countries, most prevalent in low socioeconomic groups, associated with commercial sex workers. In the United States socioeconomic status has not been found to be a factor in the spread of sexually transmitted diseases.

Chancroid, caused by H. ducreyi has infrequently been associated with cases of Genital Ulcer Disease in the US, but has been isolated in up to 10% of genital ulcers diagnosed from STD clinics in Memphis and Chicago.

Infection levels are very low in the Western world, typically around one case per two million of the population (Canada, France, Australia, UK and US). Most individuals diagnosed with chancroid have visited countries or areas where the disease is known to occur frequently, although outbreaks have been observed in association with crack cocaine use and prostitution.

Chancroid is a risk factor for contracting HIV, due to their ecological association or shared risk of exposure, and biologically facilitated transmission of one infection by the other.

Venous ulcers (venous insufficiency ulceration, stasis ulcers, stasis dermatitis, varicose ulcers, or ulcus cruris) are wounds that are thought to occur due to improper functioning of venous valves, usually of the legs (hence leg ulcers). They are the major occurrence of chronic wounds, occurring in 70% to 90% of leg ulcer cases. Venous ulcers develop mostly along the medial distal leg, and can be very painful with significant effects on quality of life.

Common organisms include Group A "Streptococcus" (group A strep), "Klebsiella", "Clostridium", "Escherichia coli", "Staphylococcus aureus," and "Aeromonas hydrophila", and others. Group A strep is considered the most common cause of necrotizing fasciitis.

The majority of infections are caused by organisms that normally reside on the individual's skin. These skin flora exist as commensals and infections reflect their anatomical distribution (e.g. perineal infections being caused by anaerobes).

Sources of MRSA may include working at municipal waste water treatment plants, exposure to secondary waste water spray irrigation, exposure to run off from farm fields fertilized by human sewage sludge or septage, hospital settings, or sharing/using dirty needles. The risk of infection during regional anesthesia is considered to be very low, though reported.

Vibrio vulnificus, a bacterium found in saltwater, is a rare cause.

Stem cell therapy may represent a treatment for promoting healing of diabetic foot ulcers. Diabetic foot ulcers develop their own, distinctive microbiota. Investigations into characterizing and identifying the phyla, genera and species of nonpathogenic bacteria or other microorganisms populating these ulcers may help identify one group of microbiota that promotes healing.