Tissue adhesives are commonly used for skin closure in both surgical and nonsurgical specialties. Although they are very well tolerated, tissue adhesives can induce a localized allergic response in 0.5% to 14% of patients. Allergic response can result in wound dehiscence, patient discomfort, increased healing time, and suboptimal esthetic results. We present two cases of allergic reaction to anterior neck incisions following topical application of tissue adhesives. The patients were managed with local wound care, steroid administration, and one with subsequent revision surgery. Clinicians who routinely use tissue adhesives should understand the incidence, risk factors, and management of allergic reaction to these products.