The management of breast tumors in women with macromastia can be challenging. Reconstructive options are limited and breast conservation therapy is often not indicated or results in poor cosmetic outcomes. The purpose of this report was to present a series of women with macromastia who underwent simultaneous reconstruction of a partial mastectomy defect with bilateral reduction mammaplasty. A retrospective review was performed and included all women who underwent partial mastectomy with simultaneous reduction mammaplasty. Data points included patient demographics, preoperative assessment, operative intervention, adjuvant treatment, and outcomes. Twenty women were included in the series (mean age, 43 years; range, 11 to 72 years) with an average body mass index of 32.6 (range, 24.9 to 44.1). Tissue diagnosis was ductal carcinoma (n = 8), ductal carcinoma in situ (n = 6), fibroadenoma (n = 4), and benign breast tissue (n = 2). The various reduction mammaplasty techniques were documented with regard to tumor size and location. The superior medial and inferior pedicles seemed to be the most versatile techniques. One patient required completion mastectomy with autologous tissue reconstruction given positive margins. All patients were disease-free at follow-up (mean, 23 months) and postoperative cancer surveillance was not impaired by the combined procedures. The versatility of reduction mammaplasty allows this procedure to be performed in conjunction with partial mastectomy for any tumor location. Combining these procedures in patients with macromastia provides numerous therapeutic benefits at low cost, while reducing breast distortion and preserving symmetry.