BACKGROUND: The quality and completeness of surgery remains critical for optimal oncological outcomes in breast cancer. A key indicator of surgical completeness is the resection margin status, which should ideally be negative, indicated by no ink on invasive tumor. However, such data is rarely reported from sub-Saharan Africa. This study aims to describe the clinical characteristics of women with non-metastatic breast cancer who underwent a mastectomy, and identify the factors influencing the resection margin status at a cancer hospital in Tanzania. METHODOLOGY: This was a retrospective cohort study analyzing clinical and pathological data of female patients, with a histologically confirmed breast cancer at stage I-III, who underwent a mastectomy at Muhimbili National Hospital in Tanzania. Data were extracted from histopathology reports and clinical records, focusing on margin status and associated variables including age, tumor size (T-status), nodal involvement (N-status), histological subtype, grade, luminal subtype, laterality, and receipt of neo-adjuvant therapy. The primary outcome was margin status post mastectomy. Descriptive statistics were used to summarize patient characteristics, and chi-square tests were applied to assess associations between variables and margin status. Statistical significance was set at p < 0.05. RESULTS: Out of the 1,020 patients analyzed, margin status was documented for 976 cases. Among these, 801 patients (82.1%) had negative margins, while 175 (17.9%) had positive or close margins; of the latter, 88.6% were positive and 11.4% close. Most patients with margin involvement (88%) had only a single margin affected. The deep margin was most frequently involved in 87% of patients with involved margins, followed by the superior margin in 57%. Margin involvement was significantly higher among younger patients, particularly those under 30 years of age (p < 0.001), and was also strongly associated with advanced T-status (p < 0.001), especially T4 tumors, where 31.7% had involved margins. No significant associations were found with histological subtype, luminal classification, laterality, receipt of neoadjuvant therapy. CONCLUSION: This study revealed a high rate of margin positivity following mastectomy, largely driven by advanced tumor stage and young age at presentation. To improve surgical outcomes in low-resource settings, we recommend interventions to improve earlier diagnosis and expanded use of neoadjuvant therapy for patients with locally advanced disease.