To determine the potential of apparent diffusion coefficient (ADC) in differentiating various sub-types of malignant and benign breast tumors using diffusion weighted MR imaging (DWI) and its association with different hormonal status in breast cancer patients.Despite the improvement in the detection of breast cancer with the widespread application of various modalities, breast lesion characterization is still challenging. DWI is used in the present study to explore the diagnostic potential of ADC in differentiating various breast tissues and characterizing breast tumors based on the differences in their hormonal receptor expression. Large cohort of 234 subjects, including 123 with locally advanced breast cancer (LABC), 61 benign and 50 normal volunteers were examined using DWI at 1.5 T. DW images were acquired in the transverse plane using a single-shot EPI sequence with TR = 5000 ms; TE= 87 ms; FOV = 250 – 350 mm; NS = 1; EPI factor =128; acquisition matrix = 128 × 128; and slice thickness = 4 to 5 mm, without any inter slice gap. Three ‘b’ values of 0, 500 and 1000 s/mm² were used. Written informed consent was obtained and Institutional ethical committee approved the study. The ER, PR, Her2neu status were available for 59 women (52.6 ± 6.4 years). 25 patients showed a positive (+) Her2neu status while 31 were Her2neu negative (-); 31 were ER+ and 28 ER-; 22 appeared with a PR + status while 34 were PR-. There were 5 triple positive (TP); 12 triple negative (TN) and 54 non-triple negative (nTN) patients. Mean ADC was calculated by drawing contiguous circular ROIs of five pixels on visible hypo-intense malignant and benign lesions, and whole breast of normal volunteer (Figure 1). ROC curve was drawn (using SPSS 16.0) to calculate a cut-off to differentiate various breast tissues. Student’s t-test was used to compare significance.The mean ADC of malignant lesions was significantly lower (1.01 ± 0.16 × 10^-3 mm²/s) than benign (1.6 ± 0.3 × 10^-3 mm²/s) and normal (1.8 ± 0.1 × 10^-3 mm²/s) breast tissues. The low ADC value is indicative of malignancy and is related to high cellularity as a result of increased cellular proliferation present in malignant tissues¹. ROC analysis carried out showed a cut-off value of 1.2 × 10^-3 mm²/s (sensitivity 91.0%; specificity 91.1%; AUC 0.98) for ADC to differentiate between malignant and benign tissues. A cut-off value of 1.5 × 10^-3 mm²/s (sensitivity 98.1%; specificity 98.4%; AUC 0.99) and a cut-off value of 1.7 × 10^-3 mm²/s (sensitivity 75.9%; specificity 74.6%; AUC 0.79) for ADC was determined to differentiate malignant versus normal and benign versus normal breast tissues, respectively (Figure 2). Our results showed a statistically lower ADC of fibroadenomas compared to fibrocystic with fibroadenoma and cystic lesions. Fibroadenomas are solid lesions and have lower microstructural complexity; therefore the water mobility is less restricted due to decreased barriers resulting into lower ADC. Further the ADC of cystic and fibrocystic lesions was significantly higher than benign ductal epithelial cells. Fibrocystic lesions show prominent cystic features, but there may not be fibrosis. Benign lesions like fibrocysts and cysts are almost full of fluid and lack capillaries, hence the diffusion of water protons occur freely without hindrance resulting into higher ADC of these lesions (Table 1). The association of ADC values with molecular biomarkers ER, PR and Her2neu was also evaluated. No variation in ADC of various tumor subtypes of breast cancer patients was seen (Table 2 and 3). Whereas, ER- patients had significantly lower age and a significantly higher mean ADC value compared to ER+ patients, which is in agreement with previous report². However, no statistical significant difference in mean ADC of TN, TP and nTN breast cancer patients was observed. The findings of the present study suggest the utility of quantitative DWI in distinguishing different types of breast tissues (malignant, benign and normal). The results showed that ADC may serve as a sensitive parameter to differentiate between different malignant and benign subtypes of breast tumors, which may have an important role in breast cancer diagnosis and treatment.