Background:  The use of acellular cadaveric dermis (ACD) in implant breast reconstruction provides an alternative to the total submuscular approach.  Clinical observations have suggested that integrated ACD exhibits different clinical and histopathologic properties than native submuscular capsule.  However, to date, there has not be any detailed analysis of the histopathologic sequelae of ACD in breast reconstruction.  Based on clinical observations, we hypothesized that the use of ACD may decrease the inflammatory response normally seen around the implant and the subsequent foreign-body capsule formation.  Methods:  Twenty-three patients underwent tissue expander reconstruction with the “dual-plane” ACD technique.  At the time of implant exchange, intraoperative biopsies were obtained: 1) the integrated ACD and 2) the native subpectoral capsule (control).  Histopathologic examination was performed.  Semi-quantitative analyses of the samples were performed with each sample being scored for granulation tissue formation, vessel proliferation, chronic inflammatory changes, capsule fibrosis, fibroblast cellularity, and foreign body giant cell inflammatory reaction.  Results:  All ACD samples were found to have statistically significant decreased levels for all parameters investigated (p < 0.0001, unpaired t-test) compared with their corresponding native breast capsules (internal controls). Conclusion: This work represents the first detailed histopathologic analysis of ACD in breast reconstruction with an internally controlled comparison to native breast capsule.  Based on these histopathologic findings, ACD may provide a method for preventing capsule formation by inhibiting inflammatory changes that are required for the inception of capsule maturation.  Further investigation is needed to determine if ACD can indeed prevent the process of capsular contracture.