Deep Vein Thrombosis (DVT): This is often the first consideration for unilateral leg swelling due to its relatively high prevalence and potential for serious complications, such as pulmonary embolism. Risk factors include recent surgery, immobilization, cancer, and genetic predispositions to clotting.

Cellulitis: A bacterial infection of the skin and subcutaneous tissues, which can cause swelling, redness, warmth, and pain in one leg. It's more common in individuals with compromised immune systems or those with a history of trauma to the affected area.
Lymphedema: Swelling caused by impaired lymph drainage, which can be primary (genetic) or secondary (due to surgery, infection, or trauma). It often presents with chronic, progressive swelling.
Venous Insufficiency: A condition where the veins have problems returning blood from the legs back to the heart due to valve issues, leading to swelling, varicose veins, and skin changes.

Compartment Syndrome: A serious condition resulting from increased pressure within a muscle compartment, which can lead to muscle and nerve damage. It's characterized by the "5 Ps": pain, pallor, pulselessness, paresthesia, and paralysis. Prompt diagnosis and treatment are crucial to prevent permanent damage.
Phlegmasia Cerulea Dolens: A severe form of DVT that causes significant swelling and cyanosis of the leg due to near-total occlusion of the venous outflow. It's a medical emergency requiring immediate anticoagulation and possibly thrombolysis.
Ruptured Baker's Cyst: Although more commonly associated with knee pain, a ruptured Baker's cyst can cause calf swelling and mimic DVT. It's essential to differentiate these conditions as their treatments vary significantly.

Lipedema: A chronic condition characterized by the abnormal growth of fat cells in the legs, leading to swelling and pain. It's often mistaken for lymphedema but does not typically respond to elevation and compression.
Filarial Lymphedema (Elephantiasis): Caused by parasitic infections (most commonly Wuchereria bancrofti), leading to severe lymphedema. It's rare in developed countries but should be considered in travelers or immigrants from endemic areas.
Klippel-Trenaunay Syndrome: A congenital condition involving vascular malformations, which can cause unilateral leg swelling, varicose veins, and skin discoloration. It's a rare condition that may be diagnosed at birth or later in life.