Breast cancer, recognized as the common cancer among women, is one of the important causes of morbidity and mortality worldwide. With regard to developments presented in screening, diagnosis, and especially therapies of this disease, survival of patients has improved in recent years, and as a result, the population at risk of complications attributable to treatment has increased, as well. Postmastectomy pain is one of the life-threatening complications of breast cancer. The nature of the mentioned pain is commonly neuropathic with abnormal sensation in intercostal nerve distribution region of upper and lateral parts of thorax, axilla, and medial and posterior parts of arm and shoulder. This pain strongly affects patients? quality of life. At present, the strongest theory about the etiology and mechanism of this phenomenon is related to the neuralgia of intercostobrachial nerve caused by the damage to the nerves after mastectomy. The type of surgery, especially complete axillary dissection (CAD), radiotherapy, chemotherapy, age, pre- and post-operative breast pain, type and size of tumor, all are considered as important risk factors. The best method for prevention and treatment of postmastectomy pain syndrome (PMPS) is multimodal approach. As the best treatment is prevention, may be prevention of this syndrome with consideration of the causative factors, timely resolution of these factors and improvement of surgery techniques could be achieved. Treatment approaches include both pharmacological interventions and non-pharmacological strategies. Pharmacotherapy is the major treatment of cancer-related pains. Intercostal nerve block, radiofrequency pulse, stellate ganglion block, neuromodulation techniques, intrathecal drug delivery, epidural injections of local anesthetic, mastopexy and use of botulinum, complementary and alternative therapies, scrambler therapy, acupuncture, yoga, and music therapy are the novel proposed strategies in this regard. Employing proper treatments can improve patients? quality of life.