Breast cancer poses a significant global health concern affecting a large number of women. Treatment strategies for breast cancer often involve the use of hormonal therapy, such as tamoxifen. However, the use of tamoxifen is associated with potential side effects, particularly in the endometrium. Objective: To evaluate the sonographic changes in the endometrium following the use of tamoxifen therapy in breast cancer patients. Methods: It was a quasi-experimental trial conducted at the Department of medical oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan from Jan 2023 to Jun 2023. Patients aged 18 years or older, histologically confirmed hormone receptor-positive breast cancer, and having tamoxifen treatment with a dose of 20mg/day for at least six months were included. Endometrial evaluation using transvaginal ultrasonography performed by experienced sonographer and sonographic parameters were assessed. Endometrial evaluation was conducted at baseline and 6 months after start of tamoxifen at regular interval as determined by the treating physician. Results: The median duration of tamoxifen therapy was 24 months with IQR as 10 to 36 months. There was statistically significant difference in pre-treatment and post-treatment endometrial thickness with p-value=0.0001. About 80.5% of the females had endometrial thickness difference of less and equal to 5mm and polyps were observed in 5 cases. Conclusions: Tamoxifen increases the risk of endometrial abnormality; this study highlights the need for monitoring endometrial changes before and after starting tamoxifen therapy in breast cancer patients to detect early suspected neoplastic changes in endometrium.