Significant cases of subcutaneous emphysema are easy to diagnose because of the characteristic signs of the condition. In some cases, the signs are subtle, making diagnosis more difficult. Medical imaging is used to diagnose the condition or confirm a diagnosis made using clinical signs. On a chest radiograph, subcutaneous emphysema may be seen as radiolucent striations in the pattern expected from the pectoralis major muscle group. Air in the subcutaneous tissues may interfere with radiography of the chest, potentially obscuring serious conditions such as pneumothorax. It can also reduce the effectiveness of chest ultrasound. On the other hand, since subcutaneous emphysema may become apparent in chest X-rays before a pneumothorax does, its presence may be used to infer that of the latter injury. Subcutaneous emphysema can also be seen in CT scans, with the air pockets appearing as dark areas. CT scanning is so sensitive that it commonly makes it possible to find the exact spot from which air is entering the soft tissues. In 1994, M.T. Macklin and C.C. Macklin published further insights into the pathophysiology of spontaneous Macklin's Syndrome occurring from a severe asthmatic attack.

The presence of subcutaneous emphysema in a person who appears quite ill and febrile after bout of vomiting followed by left chest pain is very suggestive of the diagnosis of Boerhaave's syndrome, which is a life-threatening emergency caused by rupture of the distal esophagus.

Pneumopericardium is a medical condition where air enters the pericardial cavity. This condition has been recognized in preterm neonates, in which it is associated with severe lung pathology, after vigorous resuscitation, or in the presence of assisted ventilation. This is a serious complication, which if untreated may lead to cardiac tamponade and death. Pneumomediastinum, which is the presence of air in the mediastinum, may mimic and also coexist with pneumopericardium.

It can be congenital, or introduced by a wound.

Subcutaneous emphysema is usually benign. Most of the time, SCE itself does not need treatment (though the conditions from which it results may); however, if the amount of air is large, it can interfere with breathing and be uncomfortable. It occasionally progresses to a state "Massive Subcutaneous Emphysema" which is quite uncomfortable and requires surgical drainage. When the amount of air pushed out of the airways or lung becomes massive, usually due to positive pressure ventilation, the eyelids swell so much that the patient cannot see. Also the pressure of the air may impede the blood flow to the areolae of the breast and skin of the scrotum or labia. This can lead to necrosis of the skin in these areas. The latter are urgent situations requiring rapid, adequate decompression. Severe cases can compress the trachea and do require treatment.

In severe cases of subcutaneous emphysema, catheters can be placed in the subcutaneous tissue to release the air. Small cuts, or "blow holes", may be made in the skin to release the gas. When subcutaneous emphysema occurs due to pneumothorax, a chest tube is frequently used to control the latter; this eliminates the source of the air entering the subcutaneous space. If the volume of subcutaneous air is increasing, it may be that the chest tube is not removing air rapidly enough, so it may be replaced with a larger one. Suction may also be applied to the tube to remove air faster. The progression of the condition can be monitored by marking the boundaries with a special pencil for marking on skin.

Since treatment usually involves dealing with the underlying condition, cases of spontaneous subcutaneous emphysema may require nothing more than bed rest, medication to control pain, and perhaps supplemental oxygen. Breathing oxygen may help the body to absorb the subcutaneous air more quickly.

The symptomatic patient may present with dyspnea, cyanosis, chest pain, pulsus paradoxus, bradycardia or tachycardia. On physical examination, the patient may have the classic “Beck’s triad” – hypotension, raised JVP and distant heart sounds, when complicated by cardiac tamponade. Extension of the mediastinal air to the subcutaneous tissues via the fascial planes may lead to subcutaneous emphysema. When air and fluid mix together in the pericardial sac, a tinkling sound superimposed over a succussion splash is heard. This is known as a “Bruit de Moulin”, which is French for “Mill–wheel” murmur. Air between the anterior parietal pericardium and the thoracic cage may also give rise to the “Hamman’s Sign” – which is a crunching sound typically heard on auscultation of the chest, but may sometimes be heard even with the unaided ear.

The mediastinum (from Medieval Latin "mediastinus", "midway") is the central compartment of the thoracic cavity surrounded by loose connective tissue, as an undelineated region that contains a group of structures within the thorax. The mediastinum contains the heart and its vessels, the esophagus, trachea, phrenic and cardiac nerves, the thoracic duct, thymus and lymph nodes of the central chest.

"Widened mediastinum/mediastinal widening" is where the mediastinum has a width greater than 6 cm on an upright PA chest X-ray or 8 cm on supine AP chest film.

A widened mediastinum can be indicative of several pathologies:

- aortic aneurysm

- aortic dissection

- aortic unfolding

- aortic rupture

- hilar lymphadenopathy

- anthrax inhalation - a widened mediastinum was found in 7 of the first 10 victims infected by anthrax ("Bacillus anthracis") in 2001.

- esophageal rupture - presents usually with pneumomediastinum and pleural effusion. It is diagnosed with water-soluble swallowed contrast.

- mediastinal mass

- mediastinitis

- cardiac tamponade

- pericardial effusion

- thoracic vertebrae fractures in trauma patients.

Arterial gas embolism (AGE) is a complication of lung barotrauma of ascent. It occurs when breathing gas is introduced to the circulation on the arterial side via lung over-pressure trauma. AGE can present in similar ways to arterial blockages seen in other medical situations. Affected people may suffer strokes, with paralysis or numbness down one side; they may suffer heart attacks; they may suffer pulmonary embolism with shortness of breath and chest pain. It is often impossible to distinguish AGE from DCS, but luckily it is rarely necessary for physicians to be able to distinguish between the two, as treatment is the same. Sometimes AGE and DCS are lumped into a single entity, Decompression Illness (DCI).

Barotrauma is injury caused by pressure effects on gas spaces. This may occur during ascent or descent. The ears are the most commonly affected body part. The most serious injury is lung barotrauma, which can result in pneumothorax, pneumomediastinum, pneumopericardium, subcutaneous emphysema, and arterial gas embolism. All divers, commercial air travelers, people traveling overland between different altitudes, and people who work in pressurized environments have had to deal with some degree of barotrauma effect upon their ears, sinuses, and other air spaces. At the most extreme, barotrauma can cause ruptured eardrums, bleeding sinuses, exploding tooth cavities, and the lung injuries described above. This is the reason why divers follow a procedure of not holding their breath during ascent. By breathing continuously, they keep the airways open and avoid pressure differences between their lungs and ambient pressure.