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.

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

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.

In its early stages, it can go unnoticed. It can be painless with slight physical changes. But the precursor tissue changes, can be noticed by the doctors.

Early stage symptoms can include persistent red or white patches, a non-healing ulcer, progressive swelling or enlargement, unusual surface changes, sudden tooth mobility without apparent cause, unusual oral bleeding or epitaxis and prolonged hoarseness.

Late stage symptoms can include an indurated area, paresthesia or dysesthesia of the tongue or lips, airway obstruction, chronic serous otitis media, otalgia, trismus, dysphagia, cervical lymphadenopathy, persistent pain or referred pain and altered vision.

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).

Around 95% of penile cancers are squamous cell carcinomas. They are classified into the following types:

- basaloid (4%)

- warty (6%)

- mixed warty-basaloid (17%)

- verrucous (8%)

- papillary (7%)

- other SCC mixed (7%)

- sarcomatoid carcinomas (1%)

- not otherwise specified (49%)

Other types of carcinomas are rare and may include small cell, Merkel cell, clear cell, sebaceous cell or basal cell tumors. Non-epithelial malignancies such as melanomas and sarcomas are even more rare.

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.

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.

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.

Oral cancer, also known as mouth cancer, is a type of head and neck cancer and is any cancerous tissue growth located in the oral cavity.

It may arise as a primary lesion originating in any of the tissues in the mouth, by metastasis from a distant site of origin, or by extension from a neighboring anatomic structure, such as the nasal cavity. Alternatively, the oral cancers may originate in any of the tissues of the mouth, and may be of varied histologic types: teratoma, adenocarcinoma derived from a major or minor salivary gland, lymphoma from tonsillar or other lymphoid tissue, or melanoma from the pigment-producing cells of the oral mucosa. There are several types of oral cancers, but around 90% are squamous cell carcinomas, originating in the tissues that line the mouth and lips. Oral or mouth cancer most commonly involves the tongue. It may also occur on the floor of the mouth, cheek lining, gingiva (gums), lips, or palate (roof of the mouth). Most oral cancers look very similar under the microscope and are called squamous cell carcinoma, but less commonly other types of oral cancer occur, such as Kaposi's sarcoma.

In 2013 oral cancer resulted in 135,000 deaths up from 84,000 deaths in 1990. Five-year survival rates in the United States are 63%.

The appearance and number of sarcoids can vary, with some horses having single or multiple lesions, usually on the head, legs, ventrum and genitalia or around a wound. The distribution pattern suggests that flies are an important factor in the formation of sarcoids. Sarcoids may resemble warts (verrucous form), small nodules (nodular form), oval hairless or scaly plaques (occult form) or very rarely, large ulcerated masses (fibroblastic form). The occult form usually presents on skin around the mouth, eyes or neck, while nodular and verrucous sarcoids are common on the groin, penile sheath or face. Fibroblastic sarcoids have a predilection for the legs, groin, eyelid and sites of previous injury. Multiple forms may also be present on an individual horse (mixed form). Histologically, sarcoids are composed of fibroblasts (collagen producing cells) that invade and proliferate within the dermis and sometimes the subcutaneous tissue but do not readily metastasize to other organs. Surgical biopsy can definitively diagnose sarcoids, but there is a significant risk of making sarcoids worse. Therefore, diagnosis based solely on clinical signs, fine-needle aspiration or complete excisional biopsy are safer choices.

It most often arises centrally in larger bronchi, and while it often metastasizes to locoregional lymph nodes (particularly the hilar nodes) early in its course, it generally disseminates outside the thorax somewhat later than other major types of lung cancer. Large tumors may undergo central necrosis, resulting in cavitation. A squamous-cell carcinoma is often preceded for years by squamous-cell metaplasia or dysplasia in the respiratory epithelium of the bronchi, which later transforms to carcinoma in situ.

In carcinoma in situ, atypical cells may be identified by cytologic smear test of sputum, bronchoalveolar lavage or samples from endobronchial brushings. However, squamous-cell carcinoma in situ is asymptomatic and undetectable on X-ray radiographs.

Eventually, it becomes symptomatic, usually when the tumor mass begins to obstruct the lumen of a major bronchus, often producing distal atelectasis and infection. Simultaneously, the lesion invades into the surrounding pulmonary substance. On histopathology, these tumors range from well differentiated, showing keratin pearls and cell junctions, to anaplastic, with only minimal residual squamous-cell features.

Squamous-cell carcinoma (SCC) is the most common cancer of the eye, periorbital area and penis, and it is the second most common cancer overall in horses, accounting for 12 to 20% of all cancers diagnosed. While SCC has been reported in horses aged 1 to 29-years, most cases occur in 8 to 15-year-old horses, making it the most common neoplasm reported in older horses. Carcinomas are tumors derived from epithelial cells and SCC results from transformation and proliferation of squames, epidermal skin cells that become keratinized. Squamous-cell carcinomas are often solitary, slow-growing tumors that cause extensive local tissue destruction. They can metastasize to other organs, with reported rates as high as 18.6%, primarily to the lymph nodes and lung.

Squamous-cell carcinoma (SCC) of the lung is a type of non-small-cell lung carcinoma and is more common in men than in women. It is closely correlated with a history of tobacco smoking, more so than most other types of lung cancer. According to the Nurses' Health Study, the relative risk of SCC is approximately 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to never-smokers. The relative risk increases to approximately 16 with a previous smoking duration of 30 to 40 years, and approximately 22 with more than 40 years.

Many of the symptoms of NSCLC can be signs of other diseases, but having chronic or overlapping symptoms may be a signal of the presence of the disease. Some symptoms are indicators of less advanced cases while some may signal that the cancer has spread. Some of the symptoms of less advanced cancer include chronic cough, coughing up blood, chest pain, hoarseness, shortness of breath, wheezing, chest pain, weight loss, and loss of appetite. A few more symptoms associated with the early progression of the disease are feeling weak, being very tired, having trouble swallowing, swelling in the face or neck, and continuous or recurring infections like bronchitis or pneumonia. Signs of more advanced cases include bone pain, nervous system changes (headache, weakness, dizziness, balance problems, seizures), jaundice, lumps near the surface of the body, numbness of extremities due to Pancoast Syndrome, and nausea, vomiting and constipation brought on by hypercalcemia. Some more of the symptoms that indicate further progression of the cancer include shortness of breath, superior vena cava syndrome, trouble swallowing, large amounts of mucus, weakness, fatigue, and hoarseness.

The most common types of NSCLC are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, but there are several other types that occur less frequently. A few of the less common types are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. All types can occur in unusual histologic variants and as mixed cell-type combinations. Non-squamous cell carcinoma almost occupy the half of NSCLC. In the tissue classification, the centural type contains about one-ninth.

Sometimes the phrase "not otherwise specified", or NOS is used generically, usually when a more specific diagnosis cannot be made. This is most often the case when a pathologist examines a small amount of malignant cells or tissue in a cytology or biopsy specimen.

Lung cancer in never-smokers is almost universally NSCLC, with a sizeable majority being adenocarcinoma.

On relatively rare occasions, malignant lung tumors are found to contain components of both SCLC and NSCLC. In these cases, the tumors should be classified as combined small cell lung carcinoma (c-SCLC), and are (usually) treated like "pure" SCLC.

Leukoplakia of the esophagus is rare compared to oral leukoplakia. The relationship with esophageal cancer is unclear because the incidence of esophageal leukoplakia is so low. It usually appears as a small, nearly opaque white lesion that may resemble early esophageal squamous cell carcinoma. The histologic appearance is similar to oral leukoplakia, with hyperkeratosis and possible dysplasia.

In the context of lesions of the mucous membrane lining of the bladder, leukoplakia is a historic term used to describe a visualized white patch which histologically represents keratinization in an area of squamous metaplasia. The symptoms may include frequency, suprapubic pain (pain felt above the pubis), hematuria (blood in the urine), dysuria (difficult urination or pain during urination), urgency, and urge incontinence. The white lesion may be seen during cystoscopy, where it appears as a whitish-gray or yellow lesion, on a background of inflamed urothelium and there may be floating debris in the bladder. Leukoplakia of the bladder may undergo cancerous changes, so biopsy and long term follow up are usually indicated.

Neuroendocrine carcinoma affects many different parts of the body.

In the cervix, it is a rare, but very aggressive form of cervical cancer. In its early stages, neuroendocrine carcinoma is asymptomatic (not showing or producing indications of a disease or other medical condition). In more advanced stages, symptoms of Neuroendocrine carcinoma of the cervix are: abnormal vaginal bleeding, increased vaginal discharge, and pelvic pain, painful urination, pain during sex, tiredness, leg swelling, and backache. When left untreated, metastasis or even death may occur.

Although often the terms "erythroplasia" and "erythroplakia" are used synonymously, some sources distinguish them, stating that the latter is maccular (flat) while the former is papular (bumpy).

Erythroplakia of the genital mucosae is often referred to as erythroplasia of Queyrat.

The most common areas in the mouth where erythroplakia is found are the floor of the mouth, buccal vestibule, the tongue, and the soft palate. It appears as a red macule or plaque with well-demarcated borders. The texture is characterized as soft and velvety. An adjacent area of leukoplakia may be found along with the erythroplakia.

Erythroplasia may also occur on the laryngeal mucosa, or the anal mucosa.

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.

There are two types of neuroendocrine carcinomas of the cervix: small-cell and large-cell.

Actinic keratoses can have various clinical presentations, often characterized as follows:

- Classic (or common): Classic AKs present as white, scaly macules, papules or plaques of various thickness, often with surrounding erythema. They are usually 2-6mm in diameter but can sometimes reach several centimeters in diameter.

- Hypertrophic (or hyperkeratotic): Hypertrophic AKs (HAKs) appear as a thicker scale or rough papule or plaque, often adherent to an erythematous base. Classic AKs can progress to become HAKs, and HAKs themselves can be difficult to distinguish from malignant lesions.

- Atrophic: Atrophic AKs lack an overlying scale, and therefore appear as a nonpalpable change in color (or macule). They are often smooth and red, and are less than 10mm in diameter.

- AK with cutaneous horn: A cutaneous horn is a keratinic projection with its height at least one-half of its diameter, often conical in shape. They can be seen in the setting of actinic keratosis as a progression of an HAK, but are also present in other skin conditions. 38–40% of cutaneous horns represent AKs.

- Pigmented AK: Pigmented AKs are rare variants that often present as macules or plaques that are tan to brown in color. They can be difficult to distinguish from a solar lentigo or lentigo maligna.

- Actinic cheilitis: When an AK forms on the lip, it is called actinic cheilitis. This usually presents as a rough, scaly patch on the lip, often accompanied by the sensation of dry mouth and symptomatic splitting of the lips.

- Bowenoid AK: Usually presents as a solitary, erythematous, scaly patch or plaque with well-defined borders. Bowenoid AKs are differentiated from Bowen's disease by degree of epithelial involvement as seen on histology.

The presence of ulceration, nodularity, or bleeding should raise concern for malignancy. Specifically, clinical findings suggesting an increased risk of progression to squamous cell carcinoma can be recognized as "IDRBEU": I (induration /inflammation), D (diameter > 1 cm), R (rapid enlargement), B (bleeding), E (erythema) and U (ulceration). AKs are usually diagnosed clinically, but because they are difficult to clinically differentiate from squamous cell carcinoma, any concerning features warrant biopsy for diagnostic confirmation.