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.

Screening methods for colon cancer depend on detecting either precancerous changes such as certain kinds of polyps or on finding early and thus more treatable cancer. The extent to which screening procedures reduce the incidence of gastrointestinal cancer or mortality depends on the rate of precancerous and cancerous disease in that population. gFOBT (guaiac fecal occult blood test) and flexible sigmoidoscopy screening have each shown benefit in randomized clinical trials. Evidence for other colon cancer screening tools such as iFOBT (immunochemical fecal occult blood test) or colonoscopy is substantial and guidelines have been issued by several advisory groups but does not include randomized studies.

In 2009 the American College of Gastroenterology (ACG) suggest that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a colonoscopy every 10 years in average-risk individuals, beginning at age 50. The ACG suggests that cancer detection tests such as any type of FOB are an alternative that is less preferred, and if a colonoscopy is declined, the FIT (fecal immunochemical test, or iFOBT) should be offered instead. Two other recent guidelines, from the US Multisociety Task Force (MSTF) and the US Preventive Services Task Force (USPSTF), while permitting immediate colonoscopy as an option, did not categorize it as preferred. The ACG and MSTF also included CT colonography every five years, and fecal DNA testing as considerations. All three recommendation panels recommended replacing any older low-sensitivity, guaiac-based fecal occult blood testing (gFOBT) with either newer high-sensitivity guaiac-based fecal occult blood testing (hs gFOBT) or fecal immunochemical testing (FIT). MSTF looked at six studies that compared high sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there was no clear difference in overall performance between these methods.

The American College of Gastroenterology has recommended the abandoning of gFOBT testing as a colorectal cancer screening tool, in favor of the fecal immunochemical test. Though the FIT test is preferred, even the guaiac FOB testing of average risk populations may have been sufficient to reduce the mortality associated with colon cancer by about 25%. With this lower efficacy, it was not always cost effective to screen a large population with gFOBT.

If colon cancer is suspected in an individual (such as in someone with an unexplained anemia) fecal occult blood tests may not be clinically helpful. If a doctor suspects colon cancer, more rigorous investigation is necessary, whether or not the test is positive.

In 2006, the Australian Government introduced the National Bowel Cancer Program which has been updated several times since; targeted screening will be done of all Australians aged over 50 to 74 by 2017–2018. Cancer Council Australia recommended that FOBT should be done every two years. Gradually government fund disbursement meant that some people are not yet eligible for the national program and should pay for a FOBT by themselves.

The Canadian Cancer Society recommends that men and women age 50 and over have a FOBT at least every 2 years.

In colon cancer screening, using only one sample of feces collected by a doctor performing a digital rectal examination is discouraged.

The use of the M2-PK Test is encouraged over gFOBT for routine screening as it may pick up tumors that are both bleeding and non bleeding. It is able to pick up 80 percent of colorectal cancer and 44 percent for adenoma > 1 centimeter, while gFOBT picks up 13 to 50 percent of colorectal cancers.

Genetic testing for mutations in DNA mismatch repair genes is expensive and time-consuming, so researchers have proposed techniques for identifying cancer patients who are most likely to be HNPCC carriers as ideal candidates for genetic testing. The Amsterdam Criteria (see below) are useful, but do not identify up to 30% of potential Lynch syndrome carriers. In colon cancer patients, pathologists can measure microsatellite instability in colon tumor specimens, which is a surrogate marker for DNA mismatch repair gene dysfunction. If there is microsatellite instability identified, there is a higher likelihood for a Lynch syndrome diagnosis. Recently, researchers combined microsatellite instability (MSI) profiling and immunohistochemistry testing for DNA mismatch repair gene expression and identified an extra 32% of Lynch syndrome carriers who would have been missed on MSI profiling alone. Currently, this combined immunohistochemistry and MSI profiling strategy is the most advanced way of identifying candidates for genetic testing for the Lynch syndrome.

Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.

After reporting a null finding from their randomized controlled trial of aspirin (acetylsalicylic acid – ASA) to prevent the colorectal neoplasia of Lynch syndrome, Burn and colleagues have reported new data, representing a longer follow-up period than reported in the initial "NEJM" paper. These new data demonstrate a reduced incidence in Lynch syndrome patients who were exposed to at least four years of high-dose aspirin, with a satisfactory risk profile. These results have been widely covered in the media; future studies will look at modifying (lowering) the dose (to reduce risk associated with the high dosage of ASA).

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.

The median age at diagnosis is 38 years. Women are at higher risk for developing breast cancer.

Apart from not smoking, the American Cancer Society recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing consumption of red and processed meat, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically. A 2014 review of research concluded that there was evidence that consumption of citrus fruits and curcumin reduced risk of pancreatic cancer, while there was possibly a beneficial effect from whole grains, folate, selenium, and non-fried fish.

In the general population, screening of large groups is not currently considered effective, although newer techniques, and the screening of tightly targeted groups, are being evaluated. Nevertheless, regular screening with endoscopic ultrasound and MRI/CT imaging is recommended for those at high risk from inherited genetics.

The 2010 WHO classification of tumors of the digestive system grades all the pancreatic neuroendocrine tumors (PanNETs) into three categories, based on their degree of cellular differentiation (from "NET G1" through to the poorly differentiated "NET G3"). The U.S. National Comprehensive Cancer Network recommends use of the same AJCC-UICC staging system as pancreatic adenocarcinoma. Using this scheme, the stage-by-stage outcomes for PanNETs are dissimilar to those of the exocrine cancers. A different TNM system for PanNETs has been proposed by the European Neuroendocrine Tumor Society.

An extensive literature has examined the clinical value of FOBT in iron deficiency anemia.

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).

Monitoring involves the provision of outpatient colonoscopy, and occasionally upper gastric tract esophagogastroduodenoscopy (EGD, to search for premalignant gastric or duodenal tumors), typically once every 1–3 years, and/or a genetic blood test to definitively confirm or deny susceptibility. A small number of polyps can often be excised (removed) during the procedure, if found, but if there are more severe signs or numbers, in patient surgery may be required.

NCBI states that when an individual is identified as having FAP, or the mutations resulting in FAP: "It is appropriate to evaluate the parents of an affected individual (a) with molecular genetic testing of APC if the disease-causing mutation is known in the proband [person first identified with the condition] or (b) for clinical manifestations of APC-associated polyposis conditions".

Because of the way familial polyposis develops, it is possible to have the genetic condition, and therefore be at risk, but have no polyps or issues so far. Therefore, an individual may be diagnosed "at risk of" FAP, and require routine monitoring, but not (yet) actually have FAP (i.e., carries a defective gene but as yet appears not to have any actual medical issue as a result of this). Clinical management can cover several areas:

- Identifying those individuals who could be at risk of FAP: usually from family medical history or genetic testing

- Diagnosis (confirming whether they have FAP)—this can be done either by genetic testing, which is definitive, or by visually checking the intestinal tract itself.

- Screening / monitoring programs involve visually examining the intestinal tract to check its healthy condition. It is undertaken as a routine matter every few years where there is cause for concern, when either (a) a genetic test has confirmed the risk or (b) a genetic test has not been undertaken for any reason so the actual risk is unknown. Screening and monitoring allows polyposis to be detected visually before it can become life-threatening.

- Treatment, typically surgery of some kind, is involved if polyposis has led to a large number of polyps, or a significant risk of cancer, or actual cancer.

Resection is sometimes a part of a treatment plan, but duodenal cancer is difficult to remove surgically because of the area that it resides in—there are many blood vessels supplying the lower body. Chemotherapy is sometimes used to try to shrink the cancerous mass. Other times intestinal bypass surgery is tried to reroute the stomach to intestine connection around the blockage.

A 'Whipple' procedure is a type of surgery that is sometimes possible with this cancer. In this procedure, the duodenum, a portion of the Pancreas (the head), and the gall bladder are usually removed, the small intestine is brought up to the Pylorus (the valve at the bottom of the stomach) and the Liver and Pancreas digestive enzymes and bile are connected to the small intestine below the Pylorus.

The removal of part of the Pancreas often requires taking Pancreatic Enzyme supplements to aid digestion. These are available in the form of capsules by prescription.

It is not unusual for a patient having received a Whipple procedure to feel perfectly well, and to lead his/her normal life without difficulty.

It is important for the procedure to be performed by a surgeon with extensive experience having done and observed the procedure, as specific competence makes a big difference.

Some patients need to be fitted with tubes to either add nutrients (feeding tubes) or drainage tubes to remove excess processed food that can not pass the blockage.

Little research is conducted on these cancers due to their relative rarity when compared to the more common colorectal cancers. APC-min mice which carry a gene deficiency corresponding to that of humans with FAP also go on to develop small intestinal tumors, though humans do not.

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.

The cancerous mass tends to block food from getting to the small intestine. If food cannot get to the intestines, it will cause pain, acid reflux, and weight loss because the food cannot get to where it is supposed to be processed and absorbed by the body.

Patients with duodenal cancer may experience abdominal pain, weight loss, nausea, vomiting, and chronic GI bleeding.

The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers:

- Strongly recommends cervical cancer screening in women who are sexually active and have a cervix at least until the age of 65.

- Recommend that Americans be screened for colorectal cancer via fecal occult blood testing, sigmoidoscopy, or colonoscopy starting at age 50 until age 75.

- Evidence is insufficient to recommend for or against screening for skin cancer, oral cancer, lung cancer, or prostate cancer in men under 75.

- Routine screening is not recommended for bladder cancer, testicular cancer, ovarian cancer, pancreatic cancer, or prostate cancer.

- Recommends mammography for breast cancer screening every two years from ages 50–74, but does not recommend either breast self-examination or clinical breast examination. A 2013 Cochrane review concluded that breast cancer screening by mammography had no effect in reducing mortality because of overdiagnosis and overtreatment.

Screens for gastric cancer using photofluorography due to the high incidence there.

Surgical removal of the stomach (gastrectomy) is typically recommended after for people after 20 years of age, and before 40 years of age.

Risk factors for small intestine cancer include:

- Crohn's disease

- Celiac disease

- Radiation exposure

- Hereditary gastrointestinal cancer syndromes: familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome

- Males are 25% more likely to develop the disease

Benign tumours and conditions that may be mistaken for cancer of the small bowel:

- Hamartoma

- Tuberculosis

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.

Chemotherapy has relatively poor curative efficacy in SRCC patients and overall survival rates are lower compared to patients with more typical cancer pathology. SRCC cancers are usually diagnosed during the late stages of the disease, so the tumors generally spread more aggressively than non-signet cancers, making treatment challenging. In the future, case studies indicate that bone marrow metastases will likely play a larger role in the diagnosis and management of signet ring cell gastric cancer.

In SRCC of the stomach, removal of the stomach cancer is the treatment of choice. There is no combination of chemotherapy which is clearly superior to others, but most active regimens include 5-Fluorouracil (5-FU), Cisplatin, and/or Etoposide. Some newer agents, including Taxol and Gemcitabine (Gemzar) are under investigation.

In a single case study of a patient with SRCC of the bladder with recurrent metastases, the patient exhibited a treatment response to palliative FOLFOX-6 chemotherapy.

There is a risk of development of cancer with fundic gland polyposis, but it varies based on the underlying cause of the polyposis. The risk is highest with congenital polyposis syndromes, and is lowest in acquired causes. As a result, it is recommended that patients with multiple fundic polyps have a colonoscopy to evaluate the colon. If there are polyps seen on colonoscopy, genetic testing and testing of family members is recommended.

In the gastric adenocarcinoma associated with proximal polyposis of the stomach (GAPPS), there is a high risk of early development of proximal gastric adenocarcinoma.

It is still unclear which patients would benefit with surveillance gastroscopy, but most physicians recommend endoscopy every one to three years to survey polyps for dysplasia or cancer. In the event of high grade dysplasia, polypectomy, which is done through the endoscopy, or partial gastrectomy may be recommended. One study showed the benefit of NSAID therapy in regression of gastric polyps, but the efficacy of this strategy (given the side effects of NSAIDs) is still dubious.