Purpose: To evaluate the utility of imaging modalities, including ultrasound, MRI, mammogram, and FDG-PET CT, in measuring tumor size reduction and predicting histopathological response in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). Methodology: Tumor size was measured using ultrasound, MRI, mammogram, and FDG-PET CT before and after NACT in 120 breast cancer patients. Changes in tumor size across imaging modalities were compared with histopathological findings, including Residual Cancer Burden (RCB) scores, to evaluate consistency and predictive value. Results: Ultrasound and MRI demonstrated the highest correlation with histological tumor size (r = 0.85 and 0.82, respectively). Mammograms, particularly in dense breast tissue, had lower accuracy and showed significant discrepancies in size reduction trends. FDG-PET CT was limited in accurately assessing size but provided complementary insights into tumor metabolic activity. The average tumor size reduction post-NACT was 13.2 mm, with the largest inconsistencies observed in tumors with complex histology, such as invasive carcinoma NST. Conclusion: Ultrasound and MRI are reliable imaging modalities for evaluating tumor size reduction in breast cancer patients undergoing NACT. While mammograms have limitations, FDG-PET CT remains a valuable adjunct for assessing tumor metabolism. Standardizing imaging protocols may further enhance consistency and predictive accuracy in evaluating treatment response.