BACKGROUND: Overexpression of connexin 43 (Cx43) is seen in chronic cutaneous wounds of humans, and downregulation of Cx43 expedites healing. Human epithelia that have received radiotherapy can also suffer from chronic wounds. Since increased expression of Cx43 was observed in murine skin following irradiation, we sought to confirm this in irradiated human neck skin because Cx43 inhibition may be a novel treatment of wounds in such tissue. METHODS: We prospectively recruited adult patients who underwent elective neck surgery between November 2017 and March 2018 in the Otorhinolaryngology Department of a tertiary hospital in Singapore. A sample size of five patients with prior radiotherapy to 25 controls without radiotherapy was planned a priori. Immunohistochemical staining of Cx43 was performed in the neck skin obtained from the patients and quantified under confocal microscopy. The association between demographic factors, comorbidities of the patients, and Cx43 expression was explored. Wound healing was assessed between 7 to 14 days postoperatively. RESULTS: Five patients received radiotherapy 9 months to 27 years before surgery. The expression of Cx43 was 94.2 vs. 146.4 pixel-area/nucleus in the epidermis with or without radiotherapy, respectively (P=0.39). The demographics and co-morbidities of the patients with or without radiotherapy were similar except for relative anemia in the patients who had radiotherapy (hemoglobin of 12.15 vs. 14.10 g/dL, P=0.02), but hemoglobin was not correlated with Cx43 expression (P=0.93). All skin incisions healed without dehiscence. CONCLUSIONS: Previous radiotherapy may not alter Cx43 expression in human neck skin. Whether the same is true for chronic radiation-induced wounds or acute radiation-induced dermatitis should be investigated.