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We are reporting two patients presented with intractable cancer pain that was treated with a novel application of an ultrasound-guided peripheral nerve block using corticosteroid. This technique offered relief to both patients whom otherwise their cancer pain was difficult to manage. The first patient developed lymphedema to the right axilla from metastatic squamous cell carcinoma. After multiple injections were deposited around the brachial plexus, lymphedema on the right axilla decreased slightly in size; however, range of motion improved post-procedure prior to his discharge one week later. In the second patient with left inguinal lymphadenopathy from metastatic left ureteral transitional cell carcinoma, there was a dramatic reduction in lymphedema in the left groin and leg as well as a considerable decrease in pain score during a two week follow-up after the peri-neural and peri-lymphatic femoral block. A 75% improvement in patient satisfaction was reported in the office visit’s questionnaire form. Corticosteroids can be used as an adjuvant to peripheral nerve block to decrease the pain secondary to lymphedema caused by the inflammatory response from metastatic cancer. This application can provide an alternative way to manage severe cancer-related pain caused by lymphedema in both upper and lower limbs.