Typically, either cytologic or histopathologic analysis of the suspected mass is done prior to initiating treatment. The commonly used diagnostic procedures for skin tumors are fine-needle aspiration cytology and tissue biopsy.

Cytology is an important tool that can help the veterinarian distinguish a tumor from inflammatory lesions. The biopsy technique used will largely depend on the tumor's size and location. Small masses are usually completely excised and sent to the pathology lab to confirm that the surrounding healthy tissues that were excised along with the tumor do not contain any cancer cells. If the tumor is larger, a small sample is removed for analysis and depending on the results, appropriate treatment is chosen. Depending on the tumor type and its level of aggressiveness, additional diagnostic tests can include blood tests to assess the pet’s overall health, chest X-rays to check for lung metastasis, and abdominal ultrasound to check for metastasis to other internal organs.

Following a visual examination and a dermatoscopic exam, or "in vivo" diagnostic tools such as a confocal microscope, the doctor may biopsy the suspicious mole. A skin biopsy performed under local anesthesia is often required to assist in making or confirming the diagnosis and in defining severity. Elliptical excisional biopsies may remove the tumor, followed by histological analysis and Breslow scoring. Incisional biopsies such as punch biopsies are usually contraindicated in suspected melanomas, because of the possibility of sampling error or local implantation causing misestimation of tumour thickness. However, fears that such biopsies may increase the risk of metastatic disease seem unfounded.

Total body photography, which involves photographic documentation of as much body surface as possible, is often used during follow-up for high-risk patients. The technique has been reported to enable early detection and provides a cost-effective approach (with any digital camera), but its efficacy has been questioned due to its inability to detect macroscopic changes. The diagnosis method should be used in conjunction with (and not as a replacement for) dermoscopic imaging, with a combination of both methods appearing to give extremely high rates of detection.

Definitive diagnosis of Merkel cell carcinoma (MCC) requires examination of biopsy tissue. An ideal biopsy specimen is either a punch biopsy or a full-thickness incisional biopsy of the skin including full-thickness dermis and subcutaneous fat. In addition to standard examination under light microscopy, immunohistochemistry (IHC) is also generally required to differentiate MCC from other morphologically similar tumors such as small cell lung cancer, the small cell variant of melanoma, various cutaneous leukemic/lymphoid neoplasms, and Ewing's sarcoma. Similarly, most experts recommend longitudinal imaging of the chest, typically a CT scan, to rule out that the possibility that the skin lesion is a cutaneous metastasis of an underlying small cell carcinoma of the lung.

Lactate dehydrogenase (LDH) tests are often used to screen for metastases, although many patients with metastases (even end-stage) have a normal LDH; extraordinarily high LDH often indicates metastatic spread of the disease to the liver.

It is common for patients diagnosed with melanoma to have chest X-rays and an LDH test, and in some cases CT, MRI, PET and/or PET/CT scans. Although controversial, sentinel lymph node biopsies and examination of the lymph nodes are also performed in patients to assess spread to the lymph nodes. A diagnosis of melanoma is supported by the presence of the S-100 protein marker.

HMB-45 is a monoclonal antibody that reacts against an antigen present in melanocytic tumors such as melanomas. It is used in anatomic pathology as a marker for such tumors. The antibody was generated to an extract of melanoma. It reacts positively against melanocytic tumors but not other tumors, thus demonstrating specificity and sensitivity. The antibody also reacts positively against junctional nevus cells but not intradermal nevi, and against fetal melanocytes but not normal adult melanocytes.

HMB-45 is nonreactive with almost all non-melanoma human malignancies, with the exception of rare tumors showing evidence of melanogenesis (e.g., pigmented schwannoma, clear cell sarcoma) or tumors associated with tuberous sclerosis complex (angiomyolipoma and lymphangiomyoma).

Standard X-rays are still acceptable and readily accessible imaging tools but their resolution and level of anatomical detail are not as good as for computed tomography (CT) scan. In order to definitively confirm cancer in the nasal cavity, a tissue biopsy should be obtained.

Dermatofibrosarcoma protuberans is diagnosed with a biopsy, when a portion of the tumor is removed for examination. In order to ensure that enough tissue is removed to make an accurate diagnosis, the initial biopsy of a suspected DFSP is usually done with a core needle or a surgical incision.

Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node. Microscopic examination by a pathologist is then necessary to identify molecular, cellular, or tissue architectural characteristics of epithelial cells.

Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis.

Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood to distant sites, tissues, or organs.

In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma "in situ", and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas).

In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options.

Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis of the malignancy.

The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon and bladder cancer staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.

The UICC/AJCC TNM systems are most often used. For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used.

Diagnosis is confirmed via biopsy of the tissue(s) suspected to be affected by SCC. For the skin, look under skin biopsy.

The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basalar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as actinic keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired.

The first step to diagnosing tonsil carcinoma is to obtain an accurate history from the patient. The physician will also examine the patient for any indicative physical signs. A few tests then, maybe conducted depending on the progress of the disease or if the doctor feels the need for. The tests include:

Fine needle aspiration, blood tests, MRI, x-rays and PET scan.

The basis of deciding the T stage depends on physical examination and imaging of the tumor.

The prognosis of EMECL is relatively good, and considerably better than most other forms of NSCLC. The skull and dura are possible sites for metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of malignant potential.

Imaging studies such as X-rays, computed tomography scans, or MRI may be required to diagnose clear-cell sarcoma together with a physical exam. Normally a biopsy is also necessary. Furthermore, a chest CT, a bone scan and positron emission tomography (PET) may be part of the tests in order to evaluate areas where metastases occur.

EMECL is staged in the same manner as other non-small cell lung carcinomas, based on the TNM (Tumor-Node-Metastasis) staging system.

It can be detected by magnetic resonance imaging (MRI), but a biopsy is required for the definitive diagnosis. MRI findings typically show a well-circumscribed mass that is dark on T1-weighted images and bright on T2-weighted images. Central necrosis is often present and identifiable by imaging, especially in larger masses.

The specific treatment will depend on the tumor's type, location, size, and whether the cancer has spread to other organs. Surgical removal of the tumor remains the standard treatment of choice, but additional forms of therapy such as radiation therapy, chemotherapy, or immunotherapy exist.

When detected early, skin cancer in cats and dogs can often be treated successfully. In many cases, a biopsy can remove the whole tumor, as long as the healthy tissues removed from just outside the tumor area do not contain any cancer cells.

The differential for OSSN includes pterygium, pingueculum, papilloma, solar keratosis, lipoma, lymphoma, chronic blepharoconjunctivitis, inflammation, melanoma, ocular pannus, pyogenic granuloma, kaposi sarcoma, keratocanthoma, mucoepidermoid carcinoma, pseudoepitheliomatous hyperplasia, and adenocarcinoma. While confocal microscopy can be used for diagnosis, biopsy is considered the standard, especially before treatment with a cytotoxic medication.

Since Merkel-cell cancer is uncommon and difficult to diagnose, patients may want a second opinion about the diagnosis and treatment plan before starting treatment. However, early diagnosis and treatment of Merkel-cell cancers are important factors in decreasing the chance of metastasis, after which it is exceptionally difficult to cure.

The number of studies focusing on the development of new targeted anticancer therapy is steadily rising, and thus there is hope that new drug regimes for patients with distant and systemic Merkel-cell carcinoma disease will be available in the near future. In particular, many study groups are looking for new strategies to target the MCV either to prevent infection or to inhibit viral-induced carcinogenesis.

Even highly advanced metastatic Merkel cell carcinoma can be responsive to PD-1 inhibitor treatment, providing promise for new chemotherapeutic and immunotherapeutic options.

The long-term outcome of squamous cell carcinomas is dependent upon several factors: the sub-type of the carcinoma, available treatments, location(s) and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, as less than 4% of Squamous cell carcinoma cases are at risk of metastasis. Some particular forms of squamous cell carcinomas have a higher mortality rate. One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%, although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality.

Treatment of small melanomas is often not necessary, but large tumors can cause discomfort and are usually surgically removed. Cisplatin and cryotherapy can be used to treat small tumors less than 3 centimeters, but tumors may reoccur. Cimetidine, a histamine stimulator, can cause tumors to regress in some horses, but may take up to 3 months to produce results and multiple treatments may be needed throughout the horse's life. There are few viable treatment options for horses with metastatic melanoma. However, gene therapy injections utilizing interleukin-12 and 18-encoding DNA plasmids have shown promise in slowing the progression of tumors in patients with metastatic melanoma.

This type of carcinoma is commonly managed by local resection, cryotherapy, topical chemotherapy, and radiotherapy. Multimodal therapy has been shown to improve both visual prognosis and survival.

Mohs micrographic surgery has become the treatment of choice for this form of cancer. When used as the primary treatment modality for sebaceous carcinoma of the eyelid, Mohs surgery is associated with significantly lower local and distant recurrence rates.

Lymphoma is the most common type of blood-related cancer in horses and while it can affect horses of all ages, it typically occurs in horses aged 4–11 years.

Antibodies may be used to determine the expression of protein markers on the surface of cancer cells. Often the expression of these antigens is similar to the tissue that the cancer grew from, so immunohistochemical testing sometimes helps to identify the source of the cancer. Individual tests often do not provide definitive answers, but sometimes patterns may be observed, suggesting a particular site of origin (e.g. lung, colon, etc.). Immunohistochemical testing suggests a single source of cancer origin in about one in four cases of CUP. However, there is a lack of definitive research data showing that treatment guided by information from immunohistochemical testing improves outcomes or long-term prognosis.

Appearance and location of the tumor is enough to identify it as a mammary tumor. Biopsy will give type and invasiveness of the tumor. In addition, newer studies showed that certain gene expression patterns are associated with malignant behaviour of canine mammary tumors.

Surgical removal is the treatment of choice, but chest x-rays should be taken first to rule out metastasis. Removal should be with wide margins to prevent recurrence, taking the whole mammary gland if necessary. Because 40 to 50 percent of dog mammary tumors have estrogen receptors, spaying is recommended by many veterinarians. A recent study showed a better prognosis in dogs that are spayed at the time of surgery or that had been recently spayed. However, several other studies found no improvement of disease outcome when spaying was performed after the tumor had developed. Chemotherapy is rarely used.

Hemangiosarcoma can cause a wide variety of hematologic and hemostatic abnormalities, including anemia, thrombocytopenia (low platelet count), disseminated intravascular coagulation (DIC); presence of nRBC, schistocytes, and acanthocytes in the blood smear; and leukocytosis with neutrophilia, left shift, and monocytosis.

A definitive diagnosis requires biopsy and histopathology. Cytologic aspirates are usually not recommended, as the accuracy rate for a positive diagnosis of malignant splenic disease is approximately 50%. This is because of frequent blood contamination and poor exfoliation. Surgical biopsy is the typical approach in veterinary medicine.