Sclerosing postirradiation panniculitis is an unusual variant of panniculitis that appears as a complication of megavoltage radiotherapy. Most patient are women with a history of breast cancer who develop nodular lesions on the anterior chest skin several months after receiving megavoltage therapy for breast carcinoma. Sclerosing postirradiation panniculitis is an unusual cutaneous complication of megavoltage radiotherapy that should be distinguished from subcutaneous metastatic disease, cellulitis, and connective tissue diseases involving the subcutaneous fat. The differential diagnosis can be established on the basis of the characteristic histopathologic features.