Quantitative or semi-quantitative analysis of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has been reported to correlate with the clinical and pathological response of tumors to preoperative treatment. This study was conceived to evaluate the correlation between hybrid (18)F-FDG PET/CT and apoptosis in breast cancer after neoadjuvant chemotherapy. Three cycles of neoadjuvant chemotherapy were given to forty-five patients with primary breast cancer proven by core needle biopsy. Hybrid PET/CT was performed before and after treatment and tumor to non-tumor radioactivity ratio (T/N) was calculated. The apoptotic index (AI) in core-cut and surgically resected samples was determined using TUNEL techniques. The mean T/N pre- and postchemotherapy was 3.23 +/- 0.63 and 2.31 +/- 0.49, respectively (p = 0.006), with the mean reduction rate below baseline of 31.18 +/- 13.18% (range, 6.4-50.8%). The mean AI pre- and post-chemotherapy was 2.81 +/- 0.76% and 17.31 +/- 6.85%, respectively (p < 0.0001). The mean AI change was 14.34 +/- 5.36% (range, 1.9-41.3%). A positive correlation was detected between the T/N reduction rate and AI change (r(s) = 0.850, p < 0.0001). At a threshold of 20% decrease from baseline in T/N, the mean AI change in the tumors with a reduction of 20% or more in T/N was 20.86 +/- 4.29%, while that in the tumors with a reduction of less than 20% in T/N was 8.59 +/- 2.87% (p < 0.0001). The sensitivity, specificity, positive and negative predictive values, and the accuracy of PET/CT for the prediction of clinical response were 90.9%, 83.3%, 93.8%, 76.9% and 92%, respectively. These data suggested that neoadjuvant chemotherapy may effectively induce apoptosis in breast tumors and decrease their glucose uptake. Hybrid PET/CT imaging appeared to be positively related to apoptosis level and therefore to be of value in predicting the response of breast cancer to neoadjuvant chemotherapy.