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The early stages of lymphedema are characterized by soft skin and pitting edema where the skin yields to finger pressure and remains temporarily pitted. Initially, the swelling may be intermittent and may be accompanied by a sense of puffiness or heaviness in the arm. At this point, lymphedema is typically highly responsive to therapy. If not treated, however, the increasing pressure of fluid accumulation causes expansion of the lymph vessels which then allows lymph to reverse flow back into the tissue. This may result in pain, redness, heating of the limb, and swelling as well as skin changes from soft, pliant skin to hard and stiff skin. At this point, the lymphedema usually does not respond to conservative treatment any more. Early lymphedema may last for a number of years but eventually will progress if ignored and untreated to become a chronic late stage condition.

As fluid begins to accumulate in the interstitial spaces, massive swelling of the lymph vessels in the limb develops. At this point, the lymphedema is described as "pitting" which means that if a finger is pressed into the skin, a depression will remain temporarily. As the condition progresses, the accumulation of protein and fluid also causes an inflammatory reaction which causes the production of fibrotic tissue (tough fibrous tissue) at which point fibrosis and induration (hardness) develop. When a finger is pressed into the skin at this point, the skin is "non-pitting" meaning that the tough tissue underneath the surface is no longer flexible.

The skin becomes thickened and develops peau d'orange, a dimpled appearance which is caused by congested dermal lymphatics. Scaly and /or warty deposits appear on the skin. The skin may also crack or furrow and where that occurs, the skin can become a site for debris and bacteria. This may cause lymphorrhea, or the leakage of lymph onto the surface of the skin.

When the lymphatic system is compromised, and fluid begins to accumulate, the lymphangions try to overcome any blockage by straining to propel the fluid forward but eventually they become overwhelmed and stop functioning. Sometimes the lymphatic system compensates by either creating new branches that connect to other lymph vessels or by increasing the functional level of existing vessels. This usually delays the appearance of symptoms.

At the point where the lymphangions are overwhelmed and can not longer propel the fluid forward, the symptoms of lymphedema being to appear. The walls of the vessels become fibrotic and clots can form which reduces any remaining function. The lymph nodes harden and shrink.

It is thought that the progression of lymphedema may be related to recurrent inflammatory episodes, sometimes caused by bacterial invasion through compromised skin. This further damages the lymphatic system which is already overwhelmed and unable to cope and results in dematolymphadenopathy - i.e., infection starts in the skin and moves inward to the lymphatics. Also, inflammatory cells in the skin produce cytokines and growth factors in response to damage to its outer layer (epidermis) and these promote and stimulate the growth of fibrotic tissue and fat. Thus, in later stages of lymphedema, enlargement is not due so much to fluid accumulation as it is to hugely increased amounts of tissue.