Macromastia, or breast hypertrophy, is a very common finding and a frequent cause of reduction mammaplasty all over the world. This study aims to examine the breast tissue specimens obtained by reduction mammaplasty in patients with macromastia in terms of the frequency of histopathological abnormalities (malignant and non-malignant lesions). In this cross-sectional, retrospective study, paraffin-embedded specimens of breast tissue after reduction mammaplasty were histopathologically reviewed in Tabriz Imam Reza Teaching Hospital in three years (2010-2013). All the specimens were sectioned, stained and examined by an adroit pathologist. One hundred ninety eight out of 271 primary specimens were eligible for this study. The mean age of the patients was 37.09 +/- 8.98 (range: 20-59) years, with mean body mass index of 27.44 +/- 3.85 (range: 21-35) kg m(-2). Based on the findings of microscopic examination, normal tissue was present in 98 cases (49.5%), all with increased content of fat. Fibrocystic change was the prominent benign entity, which was reported in 47.5% of the cases. Intraductal papilloma was detected 2 cases (1%). There were 4 cases with malignant lesions (2%), including 2 cases (1%) with invasive ductal carcinoma (age: 22 and 31 years old) and 2 cases (1%) with lobular carcinoma in situ (age: 21 and 35 years old). Considering the intraductal papilloma as a premalignant condition, the total rate of non-benign lesions reached to 3%. Based on the results of the present study, macromastia may be considered as a risk factor of breast malignancy. Thorough histopathological examination of the breast specimens after reduction mammaplasty, as well as strict screening of the women with nonsurgical macromastia is highly recommended.