The most common and accurate way of diagnosing an individual with this anomaly is by MRCP (Magnetic Resonance Cholangiopancreatography) or ERCP (Endoscopic Retrograde Cholangiopancreatography). This test can demonstrate the presence of two separately draining ducts within the pancreas. Other tests can assist doctors with diagnosis, such as a CT scan and an MRI.

Pleural or ascitic fluid should be sent for analysis. An elevated amylase level, usually > 1,000 IU/L, with protein levels over 3.0 g/dL is diagnostic. Serum amylase is often elevated as well, due to enzyme diffusion across the peritoneal or pleural surface. Contrast-enhanced computed tomography and endoscopic retrograde cholangiopancreatography (ERCP) may also assist in diagnosis, with the latter an essential component of treatment.

Postnatal diagnostic procedures include abdominal x-ray and ultrasound, CT scan, and upper GI and small bowel series.

Treatment of accessory pancreas depends on the location and extent of the injured tissue. Surgery may be an option, or some physicians order prophylactic antibiotics.

Pancreas divisum in individuals with no symptoms does not require treatment. Treatment of those with symptoms varies and has not been well established. A surgeon may attempt a sphincterotomy by cutting the minor papilla to enlarge the opening and allow pancreatic enzymes to flow normally. During surgery, a stent may be inserted into the duct to ensure that the duct will not close causing a blockage. This surgery can cause pancreatitis in patients, or in rare cases, kidney failure and death.

An association with adenoma of the minor papilla has been reported.

Pancreatic disorders are often accompanied by weakness and fatigue. The past Medical history may reveal previous disorders of the biliary tract or duodenum, abdominal trauma or surgery, and metabolic disorders such as diabetes mellitus. The medication history should be detailed and specifically include the use of thiazides, furosemide, estrogens, corticosteroids, sulfonamides, and opiates. Note a family history of pancreatic disorders. In the review of systems, obtain a complete description of any pain in the upper abdomen or epigastric area. Symptoms that may be important in relation to pancreatic disorders are pruritus, abdominal pain, dyspnea, nausea, and vomiting. The functional assessment includes data about the patient’s dietary habits and use of alcohol.

Note any restlessness, flushing, or diaphoresis during the examination. Vital signs may disclose low-grade fever, tachypnea, tachycardia, and hypotension. Inspect the skin for jaundice. Assess the abdomen for distention, tenderness, discoloration, and diminished bowel sounds.

Tests and procedures used to diagnose pancreatic disorders include laboratory analyses of blood, urine, stool, and pancreatic fluid, and imaging studies. Specific blood studies used to assess pancreatic function include measurements of serum amylase, lipase, glucose, calcium, and triglyceride levels. Urine amylase and renal amylase clearance tests may also be ordered. Stool specimens may be analyzed for fat content. The secretin stimulation test measures the bicarbonate concentration of pancreatic fluid after secretin is given intravenously to stimulate the production of pancreatic fluid.

Treatment usually is bypassing the obstructed segment of duodenum by duodeno-jejunostomy. Another approach is laparoscopic gastrojejunostomy or duodenojejunostomy.

Diagnosis of Pancreatic pseudocyst can be based on cyst fluid analysis:

- Carcinoembryonic antigen (CEA) and CEA-125 (low in pseudocysts and elevated in tumors);

- Fluid viscosity (low in pseudocysts and elevated in tumors);

- Amylase (usually high in pseudocysts and low in tumors)

The most useful imaging tools are:

- Ultrasonography – the role of ultrasonography in imaging the pancreas is limited by patient habitus, operator experience and the fact that the pancreas lies behind the stomach (and so a gas-filled stomach will obscure the pancreas).

- Computerized tomography – this is the gold standard for initial assessment and follow-up.

- Magnetic resonance cholangiopancreatography (MRCP) – to establish the relationship of the pseudocyst to the pancreatic ducts, though not routinely used

For diagnosis, measures of liver biochemistry and pancreatic enzymes are performed. Along with ruling out structural abnormalities, normally by performing an abdominal ultrasound and endoscopic retrograde cholangiopancreatography (ERCP). Measurements of bile transit when performing ERCP are taken to help evaluate different treatment options.

Sphincter of Oddi dysfunction is best diagnosed using manometry-an internal test done to measure the pressures within surrounding ducts to determine whether or not the muscle is functioning normally.

The production of pancreatic enzymes is suppressed by restricting the patient's oral intake of food patient in conjunction with the use of long-acting somatostatin analogues. The patient's nutrition is maintained by total parenteral nutrition.

This treatment is continued for 2–3 weeks, and the patient is observed for improvement. If no improvement is seen, the patient may receive endoscopic or surgical treatment. If surgical treatment is followed, an ERCP is needed to identify the site of the leak.

Fistulectomy is done in which the involved part of the pancreas is also removed.

Hemosuccus pancreaticus, also known as pseudohematobilia or Wirsungorrhage, is a rare cause of hemorrhage in the gastrointestinal tract. It is caused by a bleeding source in the pancreas, pancreatic duct, or structures adjacent to the pancreas, such as the splenic artery, that bleed into the pancreatic duct. Patients with hemosuccus may develop symptoms of gastrointestinal hemorrhage, such as blood in the stools, maroon stools, or melena. They may also develop abdominal pain. Hemosuccus pancreaticus is associated with pancreatitis, pancreatic cancer and aneurysms of the splenic artery. Angiography may be used to diagnose hemosuccus pancreaticus, where the celiac axis is injected to determine the blood vessel that is bleeding. Concomitant embolization of the end vessel may terminate the hemorrhage. Alternatively, a distal pancreatectomy may be required to stop the hemorrhage.

X-ray computed tomography (CT scan) findings of cysts in the pancreas are common, and often are benign. In a study of 2,832 patients without pancreatic disease, 73 patients (2.6%) had cysts in the pancreas. About 85% of these patients had a single cyst. Cysts ranged in size from 2 to 38 mm (mean, 8.9 mm). There was a strong correlation between the presence of cysts and age. No cysts were identified among patients less than 40 years of age, while 8.7 percent of the patients aged 80 to 89 years had a pancreatic cyst.

Cysts also may be present due to intraductal papillary mucinous neoplasm.

Computed tomography (CT) findings in AIP include a "diffusely enlarged hypodense" pancreas or a focal mass that may be mistaken for a pancreatic malignancy. A low-density, "capsule-like rim on CT" (possibly corresponding to an inflammatory process involving peripancreatic tissues) is thought to be an additional characteristic feature (thus the mnemonic: "sausage-shaped"). Magnetic resonance imaging (MRI) reveals a diffusely decreased signal intensity and delayed enhancement on dynamic scanning. The characteristic ERCP finding is segmental or diffuse irregular narrowing of the main pancreatic duct, usually accompanied by an extrinsic-appearing stricture of the distal bile duct. Changes in the extrapancreatic bile duct similar to those of primary sclerosing cholangitis (PSC) have been reported.

The role of endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of AIP is not well described, and EUS findings have been described in only a small number of patients. In one study, EUS revealed a diffusely swollen and hypoechoic pancreas in 8 of the 14 (57%) patients, and a solitary, focal, irregular mass was observed in 6 (46%) patients. Whereas EUS-FNA is sensitive and specific for the diagnosis of pancreatic malignancy, its role in the diagnosis of AIP remains unclear.

Intraductal papillary mucinous neoplasms can come to clinical attention in a variety of different ways. The most common symptoms include abdominal pain, nausea and vomiting. The most common signs patients have when they come to medical attention include jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), weight loss, and acute pancreatitis. These signs and symptoms are not specific for an intraductal papillary mucinous neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have an intraductal papillary mucinous neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal dilatation of the pancreatic duct or one of the branches of the pancreatic duct. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

IPMN forms cysts (small cavities or spaces) in the pancreas. These cysts are visible in CT scans (X-ray computed tomography). However, many pancreatic cysts are benign (see Pancreatic disease).

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (i.e. undergoing an ultrasound, CT or MRI scan) for another reason. Up to 6% of patients undergoing pancreatic resection did so for treatment of incidental IPMNs.

In 2011, scientists at Johns Hopkins reported that they have developed a gene-based test that can be used to distinguish harmless from precancerous pancreatic cysts. The test may eventually help patients with harmless cysts avoid needless surgery. Bert Vogelstein and his colleagues discovered that almost all of the precancerous cysts (intraductal papillary mucinous neoplasms) of the pancreas have mutations in the KRAS and/or the GNAS gene. The researchers then tested a total of 132 intraductal papillary mucinous neoplasms for mutations in KRAS and GNAS. Nearly all (127) had mutations in GNAS, KRAS or both. Next, the investigators tested harmless cysts such as serous cystadenomas, and the harmless cysts did not have GNAS or KRAS mutations. Larger numbers of patients must be studied before the gene-based test can be widely offered.

Serous cystic neoplasms can come to clinical attention in a variety of ways. The most common symptoms are very non-specific and include abdominal pain, nausea and vomiting. In contrast to many of the other tumors of the pancreas, patients rarely develop jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), or weight loss. These signs and symptoms are not specific for a serous cystic neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have serous cystic neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal a cystic mass within the pancreas. The cysts do not communicate with the larger pancreatic ducts. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (x-rayed) for another reason.

Medication (to prevent spasms) or Sphincterotomy (surgical procedure to cut the muscle) are the standard treatments for sphincter of Oddi dysfunction. One or the other may be better based on the classification of the condition.

Pancreatic pseudocyst treatment should be aimed at avoiding any complication (1 in 10 cases become infected). They also tend to rupture, and have shown that larger cysts have a higher likelihood to become more symptomatic, even needing surgery. If no signs of infection are present, initial treatment can include conservative measures such as bowel rest (NPO), parenteral nutrition (TPN), and observation. Serum amylase levels can be trended. If symptoms do not improve by 6 weeks, surgical intervention may be appropriate.

In the event of surgery:

- Cystogastrostomy: In this surgical procedure a connection is created between the back wall of the stomach and the cyst such that the cyst drains into the stomach.

- Cystjejunostomy: In this procedure a connection is created between the cyst and the small intestine so that the cyst fluid directly into the small intestine.

- Cystduodenostomy: In this procedure a connection is created between the duodenum (the first part of the intestine) and the cyst to allow drainage of the cyst content into duodenum. The type of surgical procedure depends on the location of the cyst. For pseudocysts that occur in the head of the pancreas a cystduodenostomy is usually performed.

Most recently the fourteenth Congress of the International Association of Pancreatology developed the International Consensus Diagnostic Criteria (ICDC) for AIP. The ICDC emphasizes five cardinal features of AIP which includes the imaging appearance of pancreatic parenchyma and the pancreatic duct, serum IgG4 level, other organ involvement with IgG4-related disease, pancreatic histology and response to steroid therapy.

In 2002, the Japanese Pancreas Society proposed the following diagnostic criteria for autoimmune pancreatitis:

For diagnosis, criterion I (pancreatic imaging) must be present with criterion II (laboratory data) and/or III (histopathologic findings).

Mayo Clinic has come up with five diagnostic criteria called HISORt criteria which stands for histology, imaging, serology, other organ involvement, and response to steroid therapy.

The diagnosis of chronic pancreatitis is based on tests on pancreatic structure and function. Serum amylase and lipase may be moderately elevated in cases of chronic pancreatitis, amylase and lipase are nearly always found elevated in the acute condition. A secretin stimulation test is considered the best test for diagnosis of chronic pancreatitis. Other tests used to determine chronic pancreatitis are serum trypsinogen, computed tomography, ultrasound and biopsy.

When chronic pancreatitis is caused by genetic factors, elevations in ESR, IgG4, rheumatoid factor, ANA and anti-smooth muscle antibody may be detected.

Zollinger–Ellison syndrome may be suspected when the above symptoms prove resistant to treatment, when the symptoms are especially suggestive of the syndrome, or when endoscopy is suggestive. The diagnosis is made through several laboratory tests and imaging studies:

- Secretin stimulation test, which measures evoked gastrin levels

- Fasting gastrin levels on at least three separate occasions

- Gastric acid secretion and pH (normal basal gastric acid secretion is less than 10 mEq/hour; in Zollinger–Ellison patients, it is usually more than 15 mEq/hour)

- An increased level of chromogranin A is a common marker of neuroendocrine tumors.

In addition, the source of the increased gastrin production must be determined using MRI or somatostatin receptor scintigraphy.

The diagnosis of hemosuccus pancreaticus can be difficult to make. Most patients who develop bleeding in the gastrointestinal tract have endoscopic procedures done to visualize the bowel in order to find and treat the source of the bleeding. With hemosuccus, the bleeding is coming from the pancreatic duct which enters into the first part of the small intestine, termed the duodenum. Typical gastroscopes used to visualize the esophagus, stomach and duodenum are designed with fiber-optic illumination that is directed in the same direction as the endoscope, meaning that visualization is in the forward direction. However, the pancreatic duct orifice is located on the side of the duodenum, meaning that it can be missed on forward-viewing endoscopy. A side-viewing endoscope (known as a "duodenoscope", or "side-viewer") used for endoscopic retrograde cholangiopancreatography (ERCP), a procedure to visualize the bile ducts and pancreatic duct on fluoroscopy, can be used to localize the bleeding to the pancreatic duct. It can be confused with bleeding from the common bile duct on endoscopy, leading to the term "pseudohematobilia".

Liver function test is normal apart from an increased serum bilirubin in the event of pancreaticobiliary reflux. Serum amylase is normal outside episodes of acute pancreatitis. It is difficult to diagnose HP because the bleeding is usually intermittent. Endoscopy is essential in ruling out other causes of upper gastrointestinal bleeding and in rare cases; active bleeding can be seen from the duodenal ampulla. Even though endoscopy may be normal, it helps to rule out other causes of upper digestive bleeding (erosive gastritis, peptic ulcers, and oesophageal and gastric fundus varices, etc.). Ultrasonography can be used to visualize pancreatic pseudocysts or aneurysm of the peripancreatic arteries. Doppler ultrasound or dynamic ultrasound has been reported to be diagnostic. Contrast-enhanced CT is an excellent modality for demonstrating the pancreatic pathology and can also demonstrate features of chronic pancreatitis, pseudocysts, and pseudoaneurysms. On precontrast CT, the characteristic finding of clotted blood in the pancreatic duct, known as the sentinel clot, is seldom seen. Computed tomography may show simultaneous opacification of an aneurysmal artery and pseudocyst or persistence of contrast within a pseudocyst after the arterial phase. Again, these findings are only suggestive of the diagnosis. Ultimately, angiography is the diagnostic reference standard. Angiography identifies the causative artery and allows for delineation of the arterial anatomy and therapeutic intervention.

In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II (Acute Physiology and Chronic Health Evaluation) indices. Most, but not all studies report that the Apache score may be more accurate. In the negative study of the APACHE-II, the APACHE-II 24-hour score was used rather than the 48-hour score. In addition, all patients in the study received an ultrasound twice which may have influenced allocation of co-interventions. Regardless, only the APACHE-II can be fully calculated upon admission. As the APACHE-II is more cumbersome to calculate, presumably patients whose only laboratory abnormality is an elevated lipase or amylase do not need assessment with the APACHE-II; however, this approach is not studied. The APACHE-II score can be calculated at www.sfar.org.

Practice guidelines state:

A 2009 study which followed 189 patients found no excess mortality despite the increased risk of pancreatic cancer.

The Ranson criteria are a clinical prediction rule for predicting the severity of acute pancreatitis. They were introduced in 1974.

The differential diagnosis for pancreatitis includes but is not limited to cholecystitis, choledocholithiasis, perforated peptic ulcer, bowel infarction, small bowel obstruction, hepatitis and mesenteric ischemia.

Diagnosis requires 2 of the 3 following criteria:

- Characteristic acute onset of epigastric or vague abdominal pain that may radiate to the back (see signs and symptoms above)

- Serum amylase or lipase levels ≥ 3 times the upper limit of normal

- An imaging study with characteristic changes. CT, MRI, abdominal ultrasound or endoscopic ultrasound can be used for diagnosis.

Amylase and lipase are 2 enzymes produced by the pancreas. Elevations in lipase are generally considered a better indicator for pancreatitis as it has greater specificity and has a longer half life.

For imaging, abdominal ultrasound is convenient, simple, non-invasive, and inexpensive. It is more sensitive and specific for pancreatitis from gallstones than other imaging modalities. However, in 25–35% of patients the view of the pancreas can be obstructed by bowel gas making it difficult to evaluate.

A contrast-enhanced CT scan is usually performed more than 48 hours after the onset of pain to evaluate for pancreatic necrosis and extrapancreatic fluid as well as predict the severity of the disease. CT scanning earlier can be falsely reassuring.

ERCP or an endoscopic ultrasound can also be used if a biliary cause for pancreatitis is suspected.