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The accumulation of fluid, a seroma, is a frequent complication of breast surgery. The present study examined the use of a cyanoacrylate adhesive, which was applied at the operative field after removal of the breast and lymph nodes. The results showed that seroma production was significantly less with cyanoacrylate adhesive. Thus, cyanoacrylate adhesive can contribute to the reduction of seromas after mastectomy and decrease the duration of postoperative drainage.The accumulation of fluid, a seroma, is a frequent complication after modified radical mastectomy or quadrantectomy with lymph node dissection. The aim of the present study was to examine whether a new adhesive material made of cyanoacrylate can effectively provide a sealing coat to tissues and thus reduce the incidence of seroma significantly.The present prospective, randomized case-control study included 128 women with a breast cancer diagnosis and scheduled for modified radical mastectomy or quadrantectomy with lymph node dissection in Thessaloniki, Greece. In 64 patients (cases), a cyanoacrylate adhesive was applied at the operative field after removal of the tumor and lymph nodes; the remaining 64 patients served as the controls.Seroma production (P = .001), drainage duration (P = .001), and drainage amount (P = .001) were all significantly less for cases than for controls. The results from a stepwise multiple regression model incorporating the use of adhesive, body mass index, tumor size, and number of infiltrated lymph nodes were significant and able to explain 51.6% of the variability in seroma amount.The results of our study have demonstrated that the cyanoacrylate adhesive can contribute to the reduction of seromas produced after mastectomy and subsequently decrease the duration of postoperative drainage and the frequency of seroma aspirations. However, because the pathogenesis of seroma formation is multifaceted and complex, further research of larger sample sizes is required to confirm the results of our study.