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Summary: Background: Augmentation mammoplasty with subpectoral prosthesis implantation is a frequent performed procedure in plastic surgery for reconstructive and aesthetic purposes. Although prosthesis implantation in a pocket under the major pectoralis muscle has been related to volumetric and functional alterations, there is not much information about the associated short- and long-term histological changes. Therefore, the aim of our study was to describe the acute and chronic histological muscle alterations associated with subpectoral prosthesis implantation. Materials and Method: We collected samples from patients with breast tissue expander (1 year after implantation) and from patients without implantation as a control group. The samples were processed for assessing their histological, histochemical and immunohistochemical properties. Results: In the control group, no relevant histological findings were identified. Additionally, in the patients with expander, we observed mild augmentation of the internalised nuclei, normal morphology, significant muscle atrophy and fibrosis, whereas in the patients with prosthesis considerable augmentation of internalised nuclei, significant muscle atrophy, fibrosis and alteration of normal muscle morphology were observed. Conclusion: Prosthesis implantation induces histological changes in the periprosthetic striated muscle. Chronic fibrosis and inflammation play key roles in this process, which should be characterised in more detail from the histological and molecular biological perspective.