Neo-adjuvant chemotherapy is used in cases of locally advanced breast cancer (LABC) aiming for local control of the disease and cosmetic breast surgery. The aim of the work: is to assess the response of LABC to neo-adjuvant chemotherapy by Tc-99m MIBI & Tc-99m (V)DMSA scintimammography in relation to histopathological evaluation. Materials & Method: 24 patients with locally advanced breast carcinoma, aged 30 to 65 years were included. Initial scintimammography using Tc-99m MIBI& Tc-99m (V) DMSA was done using 20 mCi of each tracer. Early images at 20 minutes as well as late images at (2 hours in case of Tc-99m MIBI & 4 hours in case of Tc-99m(V)DMSA) were acquired. After 3-4 courses of neo-adjuvant chemotherapy, scintimammography was repeated using both tracers. All the images were assessed qualitatively according to grade of uptake & quantitatively by drawing region of interest over the breast lesion and a mirror image over the contra-lateral normal breast. L/N ratio was calculated for each image. The degree of change in Tc-99m MIBI & Tc-99m (V)DMSA uptake from pre-therapy scan to post-therapy scan was calculated. Correlation between the degree of change of Tc-99m MIBI & Tc-99m(V)DMSA and histopathological percentage of necrosis, antibody expression for angiogenesis& MDR were done. Results: Good response was evident in 9 patients, 88.8% of them showed significant degree of change in Tc-99mMIBI uptake ratio, while only 33.4% showed partial degree of change in Tc-99m(V)DMSA uptake ratio. The percentage of change in Tc-99mMIBI uptake in this group ranged from 43% to 58% with mean value of 51.6%, while that of Tc-99m(V)DMSA ranged from -9.2% to 18% with mean value of -2.4%. Partial response was evident in 5 patients. All of them showed partial degree of change in Tc-99mMIBI uptake while Tc-99m(V)DMSA uptake showed no change in all the five patients. The degree of change of Tc-99mMIBI ranged from 4 %to 46% with mean value of 19.7%, while that of Tc-99m(V)DMSA ranged from -5.5% to -19.9% with mean value of -12.4%. Bad response: 10 patients showed bad response. All the ten patients showed no change in Tc-99mMIBI uptake ratio, while 50% showed no changed in Tc-99m(V)DMSA uptake ratio. The percentage of degree of change in Tc-99mMIBI ranged from-12% to 17% with mean of 2.59, while that of Tc-99m(V)DMSA ranged from -25 to 5.2 with mean value of -6.7 There was highly statistically significant correlation between degree of change of Tc-99m MIBI & percentage of histopathologic necrosis, angiogenesis as well as antibody expression against MDR (P < 0.01), whereas no significant correlation was found between degree of change of Tc-99m(V)DMSA &percentage of necrosis, angiogenesis and expression of MDR (P > 0.05).