Breast cancer is a prevalent malignancy requiring mastectomy for various indications. Understanding the disease spectrum in mastectomy cases is essential for improving patient outcomes and treatment strategies. This retrospective observational study was conducted at a tertiary care hospital from April 2023 to April 2024. We analyzed records of all patients who underwent mastectomy during this period. Data on demographics, clinical indications, and histopathological findings were extracted and analyzed using SPSS software. Descriptive statistics were used for quantitative variables, and qualitative variables were presented as numbers and percentages. A total of 184 mastectomy cases were included, with 182 (98.9%) females and two (1.1%) males. The mean age was 42.5 ± 18.8 years. Among the cases, 107 (58.2%) received neoadjuvant therapy. Pathologies included invasive breast carcinoma (65.8%), ductal carcinoma in situ (7.6%), phyllodes tumor (6.5%), and no residual tumor post-neoadjuvant therapy (20.1%). Most invasive breast carcinomas were grade 2 (69.4%) and T2 stage (47.1%), with 69.4% showing nodal involvement. The predominant histological subtype was invasive ductal carcinoma (92.6%). Molecular classifications were luminal B (42.9%), Her2 enriched (26.5%), and triple-negative (16.5%). Phyllodes tumors were benign (33.3%), borderline (25%), and malignant (41.7%). DCIS cases were mostly high nuclear grade (64.3%). This study highlights the diverse spectrum of breast diseases necessitating mastectomy, emphasizing the need for improved screening, early detection, and personalized treatment. Future research should focus on tracking outcomes and exploring factors contributing to this disease spectrum.