Poorly controlled postoperative pain is strongly associated with the development of chronic pain. We aimed to investigate the effect of topical morphine (in 1 of 3 doses: 5, 10, or 15 mg) on acute and chronic neuropathic pain after modified radical mastectomy for cancer breast. Methods: In this registered clinical trial (ClinicalTrials.gov identifier: NCT02462577), 90 patients were allocated to receive 10 mL plain bupivacaine 0.5% plus either 5, 10, or 15 mg morphine (designated by the group namesMorphine5,Morphine10, andMorphine15, respectively). The combination was diluted by saline 0.9% to 20 mL and irrigated in the wound before skin closure. Groups were compared for the following: time to first postoperative analgesia; intravenous patient-controlled analgesia (PCA) morphine consumption; pain scores; hemodynamics; sedation; adverse events in first postoperative 48 hours; and Leeds Assessment of Neuropathic Symptoms and Signs scores in first and third postoperative months. Results: No patient in theMorphine15 group requested postoperative PCA morphine versus 19 and 8 in the Morphine5 andMorphine10 groups, respectively (P 0.002). Time to first analgesic request and total consumption of PCA morphine analgesia were 7.31 ± 3.12 hours versus 14.00 ± 3.54 hours (P 0.000) and 1.42 ± 0.50 mg versus 1.00 ± 0.00 mg (P = 0.371) in the Morphine5 and Morphine10 groups, respectively. Lowest scores on visual analog pain scale at rest (P 0.001) and visual analog pain scale during movement (P 0.01) were recorded in the Morphine15 group, followed by Morphine10 then Morphine5 group. Lowest Leeds Assessment of Neuropathic Symptoms and Signs scores were recorded in the Morphine15 group in the first month (1.10 ± 0.37 vs 5.76 ± 3.26 and 4.73 ± 2.87, P 0.0001) and third postoperative month (4.40 ± 1.77 vs 6.33 ± 3.21 and 5.43 ± 2.67, P 0.006) compared with Morphine5 and Morphine10 groups, respectively. No patient in the Morphine15 group developed chronic pain versus 4 and 2 in Morphine5 and Morphine10 groups, respectively. Conclusions: Topicalmorphine controlled acute postmastectomy pain in a dose-dependent manner and reduced the incidence and severity of chronic postmastectomy pain syndrome. (Reg Anesth Pain Med 2016;41: 704–710) The skin over my incision feels as if it has been rubbed off with a metal brush. I can’t bear the touch of clothes or even the sheet. My upper arm feels as if all the skin has been peeled off. Some days, it hurts just to breathe