Esophageal cancer may be due to either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used.

Most bladder cancer is transitional cell, but bladder cancer associated with Schistosomiasis is often squamous cell carcinoma.

Cancer can be considered a very large and exceptionally heterogeneous family of malignant diseases, with squamous cell carcinomas comprising one of the largest subsets.

Conjunctival Squamous Cell Carcinoma (Conjunctival SCC) and corneal intraepithelial neoplasia comprise what are called Ocular Surface Squamous Cell Neoplasias. SCC is the most common malignancy of the conjunctiva in the US, with a yearly incidence of 1-2.8 per 100,000. Risk factors for the disease are exposure to sun (specifically occupational), exposure to UVB, and light-colored skin. Other risk factors include radiation, smoking, HPV, arsenic, and exposure to polycyclic hydrocarbons.

Conjunctival SCC is often asymptomatic at first, but it can present with the presence of a growth, red eye, pain, itching, burning, tearing, sensitivity to light, double vision, and decreased vision.

Spread of conjunctival SCC can occur in 1-21% of cases, with the first site of spread being the regional lymph nodes. Mortality for conjunctival SCC ranges from 0-8%.

Diagnosis is often made by biopsy, as well as CT (in the case of invasive SCC).

Treatment of Conjunctival SCC is usually surgical excision followed by cryotherapy. After this procedure, Conjunctival SCC can recur 8-40% of the time. Radiation treatment, topical Mitomycin C, and removal of the contents of the orbit, or exenteration, are other methods of treatment. Close follow-up is recommended, because the average time to recurrence is 8–22 months.

Penile cancer arises from precursor lesions, which generally progress from low-grade to high-grade lesions. For HPV related penile cancers this sequence is as follows:

- A. Squamous hyperplasia;

- B. Low-grade penile intraepithelial neoplasia (PIN);

- C. High-grade PIN (carcinoma in situ—Bowen's disease, Erythroplasia of Queyrat and bowenoid papulosis (BP));

- D. Invasive Carcinoma of the Penis.

However, in some cases non-dysplastic or mildly dysplastic lesions may progress directly into cancer. Examples include flat penile lesions (FPL) and condylomata acuminata.

In HPV negative cancers the most common precursor lesion is lichen sclerosus (LS).

Like many malignancies, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which a cancer spreads in the body. Much less often it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The staging of penile cancer is determined by the extent of tumor invasion, nodal metastasis, and distant metastasis.

The T portion of the AJCC TNM staging guidelines are for the primary tumor as follows:

- TX: Primary tumor cannot be assessed.

- T0: No evidence of primary tumor.

- Tis: Carcinoma "in situ".

- Ta: Noninvasive verrucous carcinoma.

- T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3–4).

- T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated.

- T2: Tumor invades the corpus spongiosum or cavernosum.

- T3: Tumor invades the urethra or prostate.

- T4: Tumor invades other adjacent structures.

Anatomic Stage or Prognostic Groups of penile cancer are as follows:

- Stage 0—Carcinoma "in situ".

- Stage I—The cancer is moderately or well differentiated and only affects the subepithelial connective tissue.

- Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra.

- Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node.

- Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes.

- Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is present.

Many malignancies can develop in vulvar structures. The signs and symptoms can include:

- Itching, burn, or bleeding on the vulva that does not go away.

- Changes in the color of the skin of the vulva, so that it looks redder or whiter than is normal.

- Skin changes in the vulva, including what looks like a rash or warts.

- Sores, lumps, or ulcers on the vulva that do not go away.

- Pain in the pelvis, especially during urination or sex.

Typically, a lesion presents in the form of a lump or ulcer on the labia majora and may be associated with itching, irritation, local bleeding or discharge, in addition to pain with urination or pain during sexual intercourse. The labia minora, clitoris, perineum and mons are less commonly involved. Due to modesty or embarrassment, patients may put off seeing a doctor.

Melanomas tend to display the typical asymmetry, uneven borders and dark discoloration as do melanomas in other parts of the body.

Adenocarcinoma can arise from the Bartholin gland and present with a painful lump.

SCC of the skin begins as a small nodule and as it enlarges the center becomes necrotic and sloughs and the nodule turns into an ulcer.

- The lesion caused by SCC is often asymptomatic

- Ulcer or reddish skin plaque that is slow growing

- Intermittent bleeding from the tumor, especially on the lip

- The clinical appearance is highly variable

- Usually the tumor presents as an ulcerated lesion with hard, raised edges

- The tumor may be in the form of a hard plaque or a papule, often with an opalescent quality, with tiny blood vessels

- The tumor can lie below the level of the surrounding skin, and eventually ulcerates and invades the underlying tissue

- The tumor commonly presents on sun-exposed areas (e.g. back of the hand, scalp, lip, and superior surface of pinna)

- On the lip, the tumor forms a small ulcer, which fails to heal and bleeds intermittently

- Evidence of chronic skin photodamage, such as multiple actinic keratoses (solar keratoses)

- The tumor grows relatively slowly

Basal cell carcinoma makes up about 1–2% of vulvar cancer. These tend to be slow-growing lesions on the labia majora but can occur anywhere on the vulva. Their behavior is similar to basal cell cancers in other locations. They often grow locally and have low risk for deep invasion or metastasis.

Treatment involves excision, but these lesions have a tendency to recur if not completely removed.

The early lesions are usually asymptomatic. The patients presenting with an advanced stage of the disease comprises around 66-77% of the cases.

The most important signs include a lump in the neck when palpated and weight loss.

People may also present with fatigue as a symptom.

The primary tumor does not have readily discernible signs or symptoms as they grow within the tonsillar capsule. It is difficult to notice anything suspicious on examination of the tonsil other than slight enlargement or the development of firmness around the area.

The carcinoma may occur in one or more sites deep within the tonsillar crypts. It may be accompanied by the enlargement of the tonsil. The affected tonsil grows into the oropharyngeal space making it noticeable by the patient in the form of a neck mass mostly in the jugulodiagastric region.

As the tonsils consist of a rich network of lymphatics, the carcinoma may metastasise to the neck lymph nodes which many are cystic.

Extension of tumor to skull or mediastinum can occur.

The additional symptoms include a painful throat, dysphagia, otalgia (due to cranial nerve involvement), foreign body sensation, bleeding, fixation of tongue (infiltration of deep muscles) and trismus (if the pterygoid muscle is involved in the parapharyngeal space).

On the other hand, the tumor may also present as a deep red or white fungating wound growing outwards, breaking the skin surface with a central ulceration. This wound-like ulcer fails to heal (non-healing) leading to bleeding and throat pain and other associated symptoms.

During biopsy, the lesion may show three signs: Gritty texture, Firmness and cystification owing to keratinization, fribrosis and necrosis respectively.

Cervical lymphydenopathy may be present.

Verrucous carcinoma (VC) is an uncommon variant of squamous cell carcinoma. This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dipper's cancer."

Most patients with verrucous carcinoma have a good prognosis. Local recurrence is not uncommon, but metastasis to distant parts of the body is rare. Patients with oral verrucous carcinoma may be at greater risk of a second oral squamous cell carcinoma, for which the prognosis is worse.

Verrucous carcinoma may occur in various head and neck locations, as well as in the genitalia. The oral cavity is the most common site of this tumor. The ages range from 50 to 80 years with a male predominance and a median age of 67 years. VC may grow large in size, resulting in the destruction of adjacent tissue, such as bone and cartilage.

The diagnosis of VC is established by close communication between surgeons and pathologists.

Surgeons must provide adequate specimens including the full thickness of the tumors and adjacent uninvolved mucosa for correct diagnoses.

Surgery is considered as the treatment of choice, but the extent of surgical margin and the adjuvant radiotherapy are still controversial.

The major risk factors are cigarette smoking and alcohol consumption, while betel nut is an additional factor in Taiwan. Different gene mutation sites in head and neck cancer between western countries and Taiwan have been reported. The presentation of VC originated from exposure to different carcinogens may not be the same.

Clear-cell adenocarcinoma is a type of adenocarcinoma that shows clear cells.

Types include:

- Clear-cell adenocarcinoma of the vagina

- Clear-cell ovarian carcinoma

- Uterine clear-cell carcinoma

- Clear-cell adenocarcinoma of the lung (which is a type of Clear-cell carcinoma of the lung)

See also:

- Clear-cell squamous cell carcinoma of the lung

Bowen's disease typically presents as a gradually enlarging, well-demarcated red colored plaque with an irregular border and surface crusting or scaling. Bowen's disease may occur at any age in adults, but is rare before the age of 30 years; most patients are aged over 60. Any site may be affected, although involvement of palms or soles is uncommon. Bowen's disease occurs predominantly in women (70–85% of cases). About 60–85% of patients have lesions on the lower leg, usually in previously or presently sun-exposed areas of skin.

This is a persistent, progressive, unelevated, red, scaly or crusted plaque which is due to an intraepidermal carcinoma and is potentially malignant. The lesions may occur anywhere on the skin surface, including on mucosal surfaces. Freezing, cauterization, or diathermy coagulation is often effective treatment. Pathomorphologic study of tissue sampling revealed: polymorphism of spiny epithelial cells has progressed into atypism; increased mitosis; giant and multinucleate cells; acanthosis; hyperkeratosis and parakeratosis; basal membrane and basal layer are retained.

The most frequent symptoms of transitional cell carcinoma are blood in the urine, painful urination, frequent urination and/or straining to urinate. This can look very similar to an infection of the urinary system.

Most cases (80%) of squamous cell carcinoma attributed to ultraviolet radiation present in areas of the skin that are usually more exposed to sunlight (e.g., head, face, neck). Although a particular form of squamous cell carcinoma, Kangri cancer is more often associated with the abdomen, thigh, and leg regions due to the usage and positioning of kangri pots, which come in close contact with these anatomical features.

Over time, the use of Kangri pots to keep warm results in erythema ab igne, a precancerous keratotic growth that “take the shape of superficial, serpegenous, reticular blackish brown colored lesions.” Eventually, the cells at the lesion site become more irregular in shape and form; the lesions “ulcerate” and may become itchy and bloody. The resulting irregular growth is the presentation of Kangri cancer.

Carcinoma of the tonsil is a type of squamous cell carcinoma. The tonsil is the most common site of squamous cell carcinoma in the oropharynx. The tumors frequently present at advanced stages, and around 70% of patients present with metastasis to the cervical lymph nodes.

The most common site for the incidence of the tumor is: the lateral wall of oropharynx 45%; base of the tongue 40%; posterior wall 10% and soft palate 5%. The most reported complaints include sore throat, otalgia or dysphagia. Some patients may complain of feeling the presence of a lump in the throat. Approximately 20% patients present with a node in the neck as the only symptom.

Main risk factors of developing carcinoma tonsil include tobacco smoking and regular intake of high amount of alcohol. It has also been linked to a virus called Human Papilloma Virus (HPV type HPV16). Other risk factors include poor maintenance of oral hygiene, a genetic predisposition leading to inclination towards development of throat cancer, immunocompromised states (such as post solid-organ transplant), and chronic exposure to agents such as asbestos and perchloroethylene in certain occupations, radiation therapy and dietary factors.

Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer, and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. Onset is often over months. Squamous-cell skin cancer is more likely to spread to distant areas than basal cell cancer.

The greatest risk factor is high total exposure to ultraviolet radiation from the Sun. Other risks include prior scars, chronic wounds, actinic keratosis, lighter skin, Bowen's disease, arsenic exposure, radiation therapy, poor immune system function, previous basal cell carcinoma, and HPV infection. Risk from UV radiation is related to total exposure, rather than early exposure. Tanning beds are becoming another common source of ultraviolet radiation. It begins from squamous cells found within the skin. Diagnosis is often based on skin examination and confirmed by tissue biopsy.

Decreasing exposure to ultraviolet radiation and the use of sunscreen appear to be effective methods of preventing squamous-cell skin cancer. Treatment is typically by surgical removal. This can be by simple excision if the cancer is small otherwise Mohs surgery is generally recommended. Other options may include application of cold and radiation therapy. In the cases in which distant spread has occurred chemotherapy or biologic therapy may be used.

As of 2015, about 2.2 million people have cSCC at any given time. It makes up about 20% of all skin cancer cases. About 12% of males and 7% of females in the United States developed cSCC at some point in time. While prognosis is usually good, if distant spread occurs five-year survival is ~34%. In 2015 it resulted in about 51,900 deaths globally. The usual age at diagnosis is around 66. Following the successful treatment of one case of cSCC people are at high risk of developing further cases.

Bowen's disease, also known as squamous cell carcinoma" in situ" is a neoplastic skin disease. It can be considered as an early stage or intraepidermal form of squamous cell carcinoma. It was named after John T. Bowen.

Erythroplasia of Queyrat is a particular type of Bowen's disease that can arise on the glans or prepuce in males, and, on the vulva in females, and may be induced by human papilloma virus. It is reported to occur in the corneoscleral limbus.

Epithelial-myoepithelial carcinoma of the lung (EMECL) is a very rare histologic form of malignant epithelial neoplasm ("carcinoma") arising from lung tissue.

In the United States, about 20-30 cases are reported each year. This may be a gross underestimate of the total number of cases as few laboratories have the reagents and expertise to make the diagnosis. The symptoms are similar to other forms of cancer and dependent on the stage. While generalized symptoms (weight loss and fatigue) may be seen, site specific symptoms are also present. If the tumor involves the head and neck region (in about 35%), then pain, a mass, obstructive symptoms, among others, may be experienced. NUT midline carcinomas are not specific to any tissue type or organ.

Common sites include the head, neck and mediastinum. The median age at diagnosis is 17 years, but older patients may be affected.

Squamous-cell skin cancer (SCC) is commonly a red, scaling, thickened patch on sun-exposed skin. Some are firm hard nodules and dome shaped like keratoacanthomas. Ulceration and bleeding may occur. When SCC is not treated, it may develop into a large mass. Squamous-cell is the second most common skin cancer. It is dangerous, but not nearly as dangerous as a melanoma.

Basal-cell skin cancer (BCC) usually presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders. Sometimes small blood vessels (called telangiectasia) can be seen within the tumor. Crusting and bleeding in the center of the tumor frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer is the least deadly and with proper treatment can be completely eliminated, often without scarring.

Bladder cancer in cats and dogs usually is transitional cell carcinoma, which arises from the epithelial cells that line the bladder. Less often, cancer of the urinary bladder is squamous cell carcinoma, adenocarcinoma, or rhabdomyosarcoma.

Keratoacanthomas (molluscum sebaceum) may be divided into the following types:

- "Giant keratoacanthomas" are a variant of keratoacanthoma, which may reach dimensions of several centimeters.

- "Keratoacanthoma centrifugum marginatum" is a cutaneous condition, a variant of keratoacanthomas, which is characterized by multiple tumors growing in a localized area.

- "Multiple keratoacanthomas" (also known as "Ferguson–Smith syndrome," "Ferguson-Smith type of multiple self-healing keratoacanthomas,") is a cutaneous condition, a variant of keratoacanthomas, which is characterized by the appearance of multiple, sometimes hundreds of keratoacanthomas.

- A "solitary keratoacanthoma" (also known as "Subungual keratoacanthoma") is a benign, but rapidly growing, locally aggressive tumor which sometimes occur in the nail apparatus.

- "Generalized eruptive keratoacanthoma" (also known as "Generalized eruptive keratoacanthoma of Grzybowski") is a cutaneous condition, a variant of keratoacanthomas, characterized by hundreds to thousands of tiny follicular keratotic papules over the entire body. Treatments are not successful for many patients with Generalized eruptive keratoacanthoma. Use of emollients and anti-itch medications can ease some symptoms. Improvement or complete resolutions of the condition has occurred with the application of the following medications: Acitretin, Isotretinoin, Fluorouracil, Methotrexate, Cyclophosphamide.

Kangri cancer is a type of squamous-cell carcinoma of the skin. It is found only in Kashmir in the northwest of the Indian subcontinent. It occurs on the lower abdomen and inner thighs and is due to the use of a kangri, a baked clay pot weaved around with wicker-work, used as a source for warmth by people in Kashmir during cold weather. One of the earliest records of the condition was described in 1881 by surgeons at the Kashmir Mission Hospital and its cause was recognized in the early 20th century as described by Arthur Neve.

Despite current knowledge of the cause of this condition, cases are still being reported.

Other conditions associated with prolonged use of the kangri in this fashion include erythema ab igne, a reticulate hypermelanosis with erythema.