People with Barrett's esophagus (a change in the cells lining the lower esophagus) are at much higher risk, and may receive regular endoscopic screening for the early signs of cancer. Because the benefit of screening for adenocarcinoma in people without symptoms is unclear, it is not recommended in the United States. Some areas of the world with high rates of squamous-carcinoma have screening programs.

To find the cause of symptoms, the doctor asks about the patient's medical history, does a physical exam, and may order laboratory studies. The patient may also have one or all of the following exams:

- Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fibre optic camera into the stomach to visualise it.

- Upper GI series (may be called barium roentgenogram).

- Computed tomography or CT scanning of the abdomen may reveal gastric cancer. It is more useful to determine invasion into adjacent tissues or the presence of spread to local lymph nodes. Wall thickening of more than 1 cm that is focal, eccentric and enhancing favours malignancy.

In 2013, Chinese and Israeli scientists reported a successful pilot study of a breathalyzer-style breath test intended to diagnose stomach cancer by analyzing exhaled chemicals without the need for an intrusive endoscopy. A larger-scale clinical trial of this technology was completed in 2014.

Abnormal tissue seen in a gastroscope examination will be biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.

Various gastroscopic modalities have been developed to increase yield of detected mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. "Endocytoscopy" involves ultra-high magnification to visualise cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are being tested investigationally for similar applications.

A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include "tripe palms" (a similar darkening hyperplasia of the skin of the palms) and the Leser-Trelat sign, which is the rapid development of skin lesions known as seborrheic keratoses.

Various blood tests may be done including a complete blood count (CBC) to check for anaemia, and a fecal occult blood test to check for blood in the stool.

Getting rid of "H. pylori" in those who are infected decreases the risk of stomach cancer, at least in those who are Asian. A 2014 meta-analysis of observational studies found that a diet high in fruits, mushrooms, garlic, soybeans, and green onions was associated with a lower risk of stomach cancer in the Korean population. Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer. A previous review of antioxidant supplementation did not find supporting evidence and possibly worse outcomes.

Staging is based on the TNM staging system, which classifies the amount of tumor invasion (T), involvement of lymph nodes (N), and distant metastasis (M). The currently preferred classification is the 2010 AJCC staging system for cancer of the esophagus and the esophagogastric junction. To help guide clinical decision making, this system also incorporates information on cell type (ESCC, EAC, etc.), grade (degree of differentiation – an indication of the biological aggressiveness of the cancer cells), and tumor location (upper, middle, lower, or junctional).

Anal Pap smears similar to those used in cervical cancer screening have been studied for early detection of anal cancer in high-risk individuals. In 2011, the HIV clinic implemented a program to enhance access to anal cancer screening for HIV-positive men. Nurse practitioners perform anal Papanicolaou screening, and men with abnormal results receive further evaluation with high-resolution anoscopy. The program has helped identify many precancerous growths, allowing them to be safely removed.

An important anatomic landmark in anal cancer is the pectinate line (dentate line), which is located about 1–2 cm from the anal verge (where the anal mucosa of the anal canal becomes skin). Anal cancers located above this line (towards the head) are more likely to be carcinomas, whilst those located below (towards the feet) are more likely to be squamous cell carcinomas that may ulcerate. Anal cancer is strongly associated with ulcerative colitis and the sexually transmissible infections HPV and HIV. Anal cancer may be a cause of constipation or tenesmus, or may be felt as a palpable mass, although it may occasionally present as an ulcerative form.

Anal cancer is investigated by biopsy and may be treated by excision and radiotherapy, or with external beam radiotherapy and adjunctive chemotherapy. The five-year survival rate with the latter procedure is above 70%.

Colorectal cancer is a disease of old age: It typically originates in the secretory cells lining the gut, and risk factors include diets low in vegetable fibre and high in fat. If a younger person gets such a cancer, it is often associated with hereditary syndromes like Peutz-Jegher's, hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis. Colorectal cancer can be detected through the bleeding of a polyp, colicky bowel pain, a bowel obstruction or the biopsy of a polyp at a screening colonoscopy. A constant feeling of having to go to the toilet or anemia might also point to this kind of cancer.

Use of a colonoscope can find these cancers, and a biopsy can reveal the extent of the involvement of the bowel wall. Removal of a section of the colon is necessary for treatment, with or without chemotherapy. Colorectal cancer has a comparatively good prognosis when detected early.

Since many, if not most, anal cancers derive from HPV infections, and since the HPV vaccine before exposure to HPV prevents infection by some strains of the virus and has been shown to reduce the incidence of potentially precancerous lesions, scientists surmise that HPV vaccination may reduce the incidence of anal cancer.

On 22 December 2010, the U.S. Food and Drug Administration approved Gardasil vaccine to prevent anal cancer and pre-cancerous lesions in males and females aged 9 to 26 years. The vaccine has been used before to help prevent cervical, vulvar, and vaginal cancer, and associated lesions caused by HPV types 6, 11, 16, and 18 in women.

The diagnosis of urachal cancer can be difficult and usually requires a multidisciplinary approach. A calcification in the midline can be detected in some patients in abdominal imaging studies. A cystoscopy is helpful in most cases. For diagnosis evaluation of a tissue biopsy is needed, which is usually obtained by transurethral resection (TURBT). Measurement of serum concentrations of CEA, CA19-9 and CA125 can be helpful in monitoring urachal cancer

After the initial diagnosis of Barrett's esophagus is rendered, affected persons undergo annual surveillance to detect changes that indicate higher risk to progression to cancer: development of epithelial dysplasia (or "intraepithelial neoplasia").

Considerable variability is seen in assessment for dysplasia among pathologists. Recently, gastroenterology and GI pathology societies have recommended that any diagnosis of high-grade dysplasia in Barrett be confirmed by at least two fellowship-trained GI pathologists prior to definitive treatment for patients. For more accuracy and reproductibility, it is also recommended to follow international classification system as the "Vienna classification" of gastrointestinal epithelial neoplasia (2000).

The median overall survival rate is about 50% in 5 years. Worse prognostic factors include the presence of residual tumor at the margin of the resection specimen (R+), invasion of the peritoneum and metastatic disease.

Avoidance of recognised risk factors (as described above) is the single most effective form of prevention. Regular dental examinations may identify pre-cancerous lesions in the oral cavity.

When diagnosed early, oral, head and neck cancers can be treated more easily and the chances of survival increase tremendously. As of 2017 it was not known if existing HPV vaccines can help prevent head and neck cancer.

The presence of goblet cells, called intestinal metaplasia, is necessary to make a diagnosis of Barrett's esophagus. This frequently occurs in the presence of other metaplastic columnar cells, but only the presence of goblet cells is diagnostic. The metaplasia is grossly visible through a gastroscope, but biopsy specimens must be examined under a microscope to determine whether cells are gastric or colonic in nature. Colonic metaplasia is usually identified by finding goblet cells in the epithelium and is necessary for the true diagnosis.

Many histologic mimics of Barrett's esophagus are known (i.e. goblet cells occurring in the transitional epithelium of normal esophageal submucosal gland ducts, "pseudogoblet cells" in which abundant foveolar [gastric] type mucin simulates the acid mucin true goblet cells). Assessment of relationship to submucosal glands and transitional-type epithelium with examination of multiple levels through the tissue may allow the pathologist to reliably distinguish between goblet cells of submucosal gland ducts and true Barrett's esophagus (specialized columnar metaplasia). Use of the histochemical stain Alcian blue pH 2.5 is also frequently used to distinguish true intestinal-type mucins from their histologic mimics. Recently, immunohistochemical analysis with antibodies to CDX-2 (specific for mid and hindgut intestinal derivation) has also been used to identify true intestinal-type metaplastic cells. The protein AGR2 is elevated in Barrett's esophagus and can be used as a biomarker for distinguishing Barrett epithelium from normal esophageal epithelium.

The presence of intestinal metaplasia in Barrett's esophagus represents a marker for the progression of metaplasia towards dysplasia and eventually adenocarcinoma. This factor combined with two different immunohistochemical expression of p53, Her2 and p16 leads to two different genetic pathways that likely progress to dysplasia in Barrett's esophagus.

These aggressive tumors are generally diagnosed at advanced stages and survival is generally shorter. The prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. One study suggests that its dismal prognosis seems to be caused by its intrinsic tumor biology, suggesting an area for further research.

Many imaging modalities are used to aid in the diagnosis of primary liver cancer. For HCC these include sonography (ultrasound), computed tomography (CT) and magnetic resonance imaging (MRI). When imaging the liver with ultrasound, a mass greater than 2 cm has more than 95% chance of being HCC. The majority of cholangiocarcimas occur in the hilar region of the liver, and often present as bile duct obstruction. If the cause of obstruction is suspected to be malignant, endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, CT, MRI and magnetic resonance cholangiopancreatography (MRCP) are used.

Tumor markers, chemicals sometimes found in the blood of people with cancer, can be helpful in diagnosing and monitoring the course of liver cancers. High levels of alpha-fetoprotein (AFP) in the blood can be found in many cases of HCC and intrahepatic cholangiocarcinoma. Cholangiocarcinoma can be detected with these commonly used tumor markers: carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). These tumour markers are found in primary liver cancers, as well as in other cancers and certain other disorders.

This disease is often discovered during surgery for other conditions, e.g., hernia repair, following which an experienced pathologist can confirm the diagnosis. Advanced stages may present as tumors palpable on the abdomen or distention of the belly ("jelly belly" is sometimes used as a slang term for the condition). Due to the rarity of this disease, it is important to obtain an accurate diagnosis so that appropriate treatment may be obtained from a surgical oncologist who specializes in appendix cancer. Diagnostic tests may include CT scans, examination of tissue samples obtained through laparoscopy, and the evaluation of tumor markers. In most cases a colonoscopy is unsuitable as a diagnostic tool because in most cases appendix cancer invades the abdominal cavity but not the colon (however, spread inside the colon is occasionally reported). PET scans may be used to evaluate high-grade mucinous adenocarcinoma, but this test is not reliable for detecting low-grade tumors because those do not take up the dye which shows up on scans. New MRI procedures are being developed for disease monitoring, but standard MRIs are not typically used as a diagnostic tool. Diagnosis is confirmed through pathology.

Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor and occurs mainly in men ages 38 to 83. However, one such patient treated with a radical cystectomy followed by combined S-1 and Cisplatin adjuvant chemotherapy did demonstrate promising long-term survival of 90 months.

Adenocarcinoma is a cancer of epithelial tissue that has glandular characteristics. Several head and neck cancers are adenocarcinomas (either of intestinal or non-intestinal cell-type).

80% of cases in the United States are diagnosed by mammography screening.

Prevention of cancers can be separated into primary, secondary, and tertiary prevention. Primary prevention preemptively reduces exposure to a risk factor for liver cancer. One of the most successful primary liver cancer preventions is vaccination against hepatitis B. Vaccination against the hepatitis C virus is currently unavailable. Other forms of primary prevention are aimed at limiting transmission of these viruses by promoting safe injection practices, screening blood donation products, and screening high-risk asymptomatic individuals. Aflatoxin exposure can be avoided by post-harvest intervention to discourage mold, which has been effective in west Africa. Reducing alcohol abuse, obesity, and diabetes would also reduce rates of liver cancer. Diet control in hemochromatosis could decrease the risk of iron overload, decreasing the risk of cancer.

Secondary prevention includes both cure of the agent involved in the formation of cancer (carcinogenesis) and the prevention of carcinogenesis if this is not possible. Cure of virus-infected individuals is not possible, but treatment with antiviral drugs such as interferon can decrease the risk of liver cancer. Chlorophyllin may have potential in reducing the effects of aflatoxin.

Tertiary prevention includes treatments to prevent the recurrence of liver cancer. These include the use of chemotherapy drugs and antiviral drugs.

Large-cell carcinoma (LCC), like small-cell carcinoma (SCC) is very rare and only accounts for about 5% of all cervical cancers. Early-stage LCC are extremely aggressive and difficult to diagnose due to the sub-mucosal location of the tumor and intact overlying mucosa. As with SCC, in LCC early cases are asymptomatic. Later stages present with irregular bleeding, vaginal spotting, discharge, and pelvic pain. The basis for treatment of LCC tumors is derived from therapy used for SCC; when diagnosed, multimodal therapy should be considered just as with SCC.

Screening by hysteroscopy to obtain cell samples obtained for histological examination is being developed. This is similar to the current pap smear that is used to detect cervical cancer. The UK Collaborative Trial of Ovarian Cancer Screening is testing a screening technique that combines CA-125 blood tests with transvaginal ultrasound. Other studies suggest that this screening procedure may be effective. However, it's not yet clear if this approach could actually help to save lives—the full results of the trial will be published in 2015. One major problem with screening is no clear progression of the disease from stage I (noninvasive) to stage III (invasive) is seen, and it may not be possible to find cancers before they reach stage III. Another problem is that screening methods tend to find too many suspicious lesions, most of which are not cancer, but malignancy can only be assessed with surgery. The ROCA method combined with transvaginal ultrasonography is being researched in high-risk women to determine if it is a viable screening method. It is also being investigated in normal-risk women as it has shown promise in the wider population. Studies are also in progress to determine if screening helps detect cancer earlier in people with BRCA mutations.

Research into various prognostic factors for ovarian cancer is also going on. Recent research shows that thrombocytosis predicts lower survival and higher stage cancer. Ongoing research is also investigating the benefits of surgery for recurrent ovarian cancer.

Treatment is variable, both due to its rarity and to its frequently slow-growing nature. Treatment ranges from watchful waiting to debulking and hyperthermic intraperitoneal chemotherapy (HIPEC, also called intraperitoneal hyperthermic chemotherapy, IPHC) with cytoreductive surgery.

Diagnosis may include a fluorescence in situ hybridization (FISH) test, computed tomography urography (CTU), magnetic resonance urography (MRU), intravenous pyelography (IVP) x-ray, ureteroscopy, or biopsy.