A subcutaneous, prepectoral, muscle-sparing approach has been recently described for implant-based breast reconstruction. This is a preliminary series of 2-stage breast reconstructions by means of tissue expander placed subcutaneously with the support of a titanium-coated polypropylene mesh. A pilot series of cases was started in 2012. Inclusion criteria were informed consent, age less than 80 years, normal body mass index (range, 18.5–24.9), no T4 and metastatic cancers, no comorbidities, and nonsmoking patients. Expander losses, infections, seromas, skin/nipple necrosis, wound dehiscence, and reinterventions were registered in follow-up visits. Furthermore, patients were followed up in second-stage procedures and for at least 1 year from implant positioning to collect any surgical complication, reinterventions, cosmetic outcome, and oncological data. Between June 2012 and March 2014, 25 cases were enrolled in the study. Expander/implant loss rate was 0%. Skin/nipple necrosis rate was 4%. Infections rate was 12% after first-stage and 4% after second-stage procedure. Seromas rate was 0%. Five (20%) fat graft procedures were performed over the expander before second-stage reconstruction, and no reinterventions were required after second stage. Patients mean score was 99 for cosmetic outcome satisfaction, in a 0–100 scale. Subcutaneous 2-stage reconstruction with synthetic mesh proved safe and feasible. Patients satisfaction is very good after 14 months median follow-up form definitive implant placement. Although the present study involved only a small number of cases, a tissue-expander subcutaneous reconstruction seems to have promising results. Whenever pectoralis major muscle can be spared, a conservative reconstruction might be an option.